Chromosome 4

Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 190 million base pairs (the building material of DNA) and represents between 6 and 6.5 percent of the total DNA in cells.

Chromosome 4
Human chromosome 4 pair after G-banding. One is from mother, one is from father.
Chromosome 4 pair in human male karyogram.
Features
Length (bp)	193,574,945 bp (CHM13)
No. of genes	727 (CCDS)[1]
Type	Autosome
Centromere position	Submetacentric[2] (50.0 Mbp[3])
Complete gene lists
CCDS	Gene list
HGNC	Gene list
UniProt	Gene list
NCBI	Gene list
External map viewers
Ensembl	Chromosome 4
Entrez	Chromosome 4
NCBI	Chromosome 4
UCSC	Chromosome 4
Full DNA sequences
RefSeq	NC_000004 (FASTA)
GenBank	CM000666 (FASTA)

Genomics

The chromosome is ~193 megabases in length. In a 2012 paper, 775 protein-encoding genes were identified on this chromosome.^[4] 211 (27.9%) of these coding sequences did not have any experimental evidence at the protein level, in 2012. 271 appear to be membrane proteins. 54 have been classified as cancer-associated proteins.

Genes

Number of genes

The following are some of the gene count estimates of human chromosome 4. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction). Among various projects, the collaborative consensus coding sequence project (CCDS) takes an extremely conservative strategy. So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes.^[5]

Estimated by	Protein-coding genes	Non-coding RNA genes	Pseudogenes	Source	Release date
CCDS	727	—	—	[1]	2016-09-08
HGNC	731	277	633	[6]	2017-05-12
Ensembl	746	993	727	[7]	2017-03-29
UniProt	765	—	—	[8]	2018-02-28
NCBI	769	934	819	[9][10][11]	2017-05-19

Gene list

See also: Category:Genes on human chromosome 4

The following is a partial list of genes on human chromosome 4. For complete list, see the link in the infobox on the right.

• AASDH: aminoadipate-semialdehyde dehydrogenase
• ACVR1: activin-like kinase 2 (ALK-2)
• ACOX3: encoding enzyme Peroxisomal acyl-coenzyme A oxidase 3
• AFAP1-AS1: encoding protein AFAP1 antisense RNA 1
• AGA: AGU syndrome (Finnish heritage disease) related gene
• AGPAT9: encoding enzyme Glycerol-3-phosphate acyltransferase 3 a.k.a. 1-acylglycerol-3-phosphate O-acyltransferase 9
• ANK2: ankyrin 2, neuronal
• APBB2: encoding protein Amyloid beta A4 precursor protein-binding family B member 2
• ART3: encoding enzyme Ecto-ADP-ribosyltransferase 3
• ASAHL: encoding enzyme N-acylethanolamine-hydrolyzing acid amidase
• BANK1: encoding protein B cell scaffold protein with ankyrin repeats 1
• BEND4: encoding protein BEN domain containing 4
• CCDC109B: Coiled-coil domain containing 109B
• CLNK: encoding protein Cytokine dependent hematopoietic cell linker
• Complement Factor I: Complement Factor I
• COL25A1-DT: encoding protein Zinc finger, cchc domain containing 23
• CRMP1: Collapsin response mediator protein 1, a member of CRMP family
• CSN2: Beta-casein
• CXCL1: chemokine (C-X-C motif) ligand 1, scyb1
• CXCL2: chemokine (C-X-C motif) ligand 2, scyb2
• CXCL3: chemokine (C-X-C motif) ligand 3, scyb3
• CXCL4: chemokine (C-X-C motif) ligand 4, Platelet factor-4, PF-4, scyb4
• CXCL5: chemokine (C-X-C motif) ligand 5, scyb5
• CXCL6: chemokine (C-X-C motif) ligand 6, scyb6
• CXCL7: chemokine (C-X-C motif) ligand 7, PPBP, scyb7
• CXCL8: chemokine (C-X-C motif) ligand 8, interleukin 8 (IL-8), scyb8
• CXCL9: chemokine (C-X-C motif) ligand 9, scyb9
• CXCL10: chemokine (C-X-C motif) ligand 10, scyb10
• CXCL11: chemokine (C-X-C motif) ligand 11, scyb11
• CXCL13: chemokine (C-X-C motif) ligand 13, scyb13
• CYTL1: Cytokine-like 1
• DCUN1D4: Defective in cullin neddylation 1 domain containing 4
• DHX15: DEAH-box helicase 15
• DKK2: Dickkopf-related protein 2
• DMAC1: encoding protein Transmembrane protein 261
• DUX4: Thought to be inactive but 2010 research shows a key role in FSHD^[12]
• ELMOD2: Elmo domain-containing 2
• EMCN: Endomucin
• EVC: Ellis–Van Creveld syndrome
• EVC2: Ellis–Van Creveld syndrome 2 (limbin)
• Factor XI: Mutations cause Haemophilia C
• FAM114A1: Family with sequence similarity 114, member A1
• FAM149A: Family with sequence similarity 149, member A
• FAM193A: Family with sequence similarity 193, member A
• FAM198B: encoding protein Protein ENED
• FAM221B: Family with sequence similarity 221, member B
• FAM47E-STBD1: FAM47E-STBD1 readthrough
• FGF2: Fibroblast growth factor 2 (basic fibroblast growth factor)
• FGFR3: fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism, bladder cancer)
• FGFRL1: fibroblast growth factor receptor-like 1
• FRG1: FSHD region gene 1
• FRYL: encoding protein FRY like transcription coactivator
• FSTL5: encoding protein Follistatin like 5
• GUF1: GUF1 homolog, GTPase
• HDL3: encoding Huntington-like neurodegenerative disorder 2 protein
• HELQ: encoding protein Helicase, POLQ-like
• HTT (Huntingtin): huntingtin protein (Huntington's disease)
• IGJ: linker protein for immunoglobulin alpha and mu polypeptides
• INTS12: Integrator complex subunit 12
• KDR: Kinase insert domain receptor (Vascular endothelial growth factor receptor 2)
• KIAA1530: UV stimulated scaffold protein A
• KIT: tyrosine-protein kinase KIT, CD117; mast/stem cell growth factor receptor (SCFR)
• LCORL: Ligand dependent nuclear receptor corepressor like
• LDB2: LIM domain-binding protein 2
• LGI2: Leucine-rich repeat LGI family member 2
• LOC100505912 encoding protein Uncharacterized LOC100505912
• LSM6: U6 snRNA-associated Sm-like protein
• LTO1P1: encoding protein Oral cancer overexpressed 1 pseudogene 1
• LYAR: Cell growth-regulating nucleolar protein
• MAB21L2: Mab-21-like 2
• Marcksl1: encoding protein MARCKS-like 1
• MAML3: Mastermind-like 3
• MFSD7: encoding protein Major facilitator superfamily domain containing 7
• MIR1269A: microRNA 1269a
• MIR95: non-coding RNA MicroRNA 95
• MLF1IP: Centromere protein U
• MMAA: methylmalonic aciduria (cobalamin deficiency) cblA type
• MTHFD2L: NAD-dependent methylenetetrahydrofolate dehydrogenase 2-like protein
• MYL5: Myosin light chain 5
• NAP1L5: encoding protein Nucleosome assembly protein 1 like 5
• NDNF: encoding protein Neuron derived neurotrophic factor
• NOA1: encoding protein Nitric oxide associated 1
• NPNT: encoding protein Nephronectin
• NUDT6: nudix hydrolase 6
• NUDT9: nudix hydrolase 9
• OTUD4: OTU domain-containing protein 4
• PABPC4L: encoding protein Poly(A) binding protein, cytoplasmic 4-like
• PARM1: Prostate androgen-regulated mucin-like protein 1
• PHOX2B: codes for a homeodomain transcription factor
• PI4K2B: Phosphatidylinositol 4-kinase type 2-beta
• PKD2: polycystic kidney disease 2 (autosomal dominant)
• PLAC8: encoding protein Placenta specific 8
• PLK4: Serine/threonine-protein kinase PLK4
• PPEF2: encoding protein Protein phosphatase with ef-hand domain 2
• PSAPL1: encoding protein Prosaposin-like 1 (gene/pseudogene)
• QDPR: quinoid dihydropteridine reductase
• RBM47: RNA binding motif protein 47
• RG9MTD2: encoding protein RNA (guanine-9-) methyltransferase domain containing 2
• SCRG1: encoding protein Stimulator of chondrogenesis 1
• SDAD1: protein SDA1 homolog
• SEC24B: Sec24 homolog B
• SEC24D: Sec24 homolog D
• SEPT11: Septin-11
• SLC9B2: solute carrier family 9 member B2
• SLC10A4: solute carrier family 10 member 4
• SMIM20: encoding protein Small integral membrane protein 20
• SNCA: synuclein, alpha (non A4 component of amyloid precursor)
• SPATA5: Spermatogenesis-associated protein 5
• STATH: gene with protein product
• TACC3: Transforming acidic coiled-coil-containing protein 3
• TENM3: Teneurin transmembrane protein 3
• THAP6: THAP domain-containing protein 6
• TMEM155: encoding protein Transmembrane protein 155
• TMEM165: encoding protein Transmembrane protein 165
• TMEM175: encoding protein Transmembrane protein 175
• TMEM243: encoding protein Transmembrane protein 243
• TMPRSS11D: Transmembrane protease, serine 11D
• TMPRSS11F: encoding protein Transmembrane serine protease 11F
• TNIP2: TNFAIP3-interaction protein 2
• TNIP3: encoding protein TNFAIP3 interacting protein 3
• UCHL1: ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
• UGDH-AS1: encoding protein UGDH antisense RNA 1
• UGT8: UDP glycosyltransferase 8
• UNC5C: netrin receptor UNC5C
• UPF0602: encoding UPF0602 Protein C4orf47
• USP38: encoding protein Ubiquitin specific peptidase 38
• USP53: ubiquitin specific peptidase 53
• UTP3: small subunit processome component
• VPS54
• WFS1: Wolfram syndrome 1 (wolframin)
• ZGRF1: zinc-finger GRF-type containing 1
• ZNF621: encoding protein Zinc finger protein 621

Diseases and disorders

The following are some of the diseases related to genes located on chromosome 4:

• Achondroplasia
• Autosomal dominant polycystic kidney disease (PKD-2)
• Bladder cancer
• Crouzonodermoskeletal syndrome
• Chronic lymphocytic leukemia
• Congenital central hypoventilation syndrome
• Ellis–Van Creveld syndrome
• Facioscapulohumeral muscular dystrophy
• Fibrodysplasia ossificans progressiva (FOP)
• Haemophilia C
• Huntington's disease
• Hemolytic uremic syndrome
• Hereditary benign intraepithelial dyskeratosis
• Hirschprung's disease
• Hypochondroplasia
• Mast cell activation syndrome
• Methylmalonic acidemia
• Mucopolysaccharidosis type I
• Muenke syndrome
• Nonsyndromic deafness
• Nonsyndromic deafness, autosomal dominant
• Parkinson's disease
• Polycystic kidney disease
• Romano–Ward syndrome
• SADDAN
• Tetrahydrobiopterin deficiency
• Thanatophoric dysplasia
  • Type 1
  • Type 2
• Wolfram syndrome
• Wolf–Hirschhorn syndrome

Cytogenetic band

G-banding ideograms of human chromosome 4

G-banding ideogram of human chromosome 4 in resolution 850 bphs. Band length in this diagram is proportional to base-pair length. This type of ideogram is generally used in genome browsers (e.g. Ensembl, UCSC Genome Browser).

G-banding patterns of human chromosome 4 in three different resolutions (400,^[13] 550^[14] and 850^[3]). Band length in this diagram is based on the ideograms from ISCN (2013).^[15] This type of ideogram represents actual relative band length observed under a microscope at the different moments during the mitotic process.^[16]

G-bands of human chromosome 4 in resolution 850 bphs^[17]

Chr.	Arm[18]	Band[19]	ISCN start[20]	ISCN stop[20]	Basepair start	Basepair stop	Stain[21]	Density
4	p	16.3	0	220	1	4,500,000	gneg
4	p	16.2	220	389	4,500,001	6,000,000	gpos	25
4	p	16.1	389	779	6,000,001	11,300,000	gneg
4	p	15.33	779	1066	11,300,001	15,000,000	gpos	50
4	p	15.32	1066	1286	15,000,001	17,700,000	gneg
4	p	15.31	1286	1557	17,700,001	21,300,000	gpos	75
4	p	15.2	1557	1811	21,300,001	27,700,000	gneg
4	p	15.1	1811	2166	27,700,001	35,800,000	gpos	100
4	p	14	2166	2505	35,800,001	41,200,000	gneg
4	p	13	2505	2742	41,200,001	44,600,000	gpos	50
4	p	12	2742	2877	44,600,001	48,200,000	gneg
4	p	11	2877	3046	48,200,001	50,000,000	acen
4	q	11	3046	3249	50,000,001	51,800,000	acen
4	q	12	3249	3571	51,800,001	58,500,000	gneg
4	q	13.1	3571	3910	58,500,001	65,500,000	gpos	100
4	q	13.2	3910	4062	65,500,001	69,400,000	gneg
4	q	13.3	4062	4333	69,400,001	75,300,000	gpos	75
4	q	21.1	4333	4502	75,300,001	78,000,000	gneg
4	q	21.21	4502	4671	78,000,001	81,500,000	gpos	50
4	q	21.22	4671	4739	81,500,001	83,200,000	gneg
4	q	21.23	4739	4874	83,200,001	86,000,000	gpos	25
4	q	21.3	4874	5145	86,000,001	87,100,000	gneg
4	q	22.1	5145	5517	87,100,001	92,800,000	gpos	75
4	q	22.2	5517	5636	92,800,001	94,200,000	gneg
4	q	22.3	5636	5890	94,200,001	97,900,000	gpos	75
4	q	23	5890	6059	97,900,001	100,100,000	gneg
4	q	24	6059	6347	100,100,001	106,700,000	gpos	50
4	q	25	6347	6685	106,700,001	113,200,000	gneg
4	q	26	6685	7040	113,200,001	119,900,000	gpos	75
4	q	27	7040	7277	119,900,001	122,800,000	gneg
4	q	28.1	7277	7565	122,800,001	127,900,000	gpos	50
4	q	28.2	7565	7734	127,900,001	130,100,000	gneg
4	q	28.3	7734	8259	130,100,001	138,500,000	gpos	100
4	q	31.1	8259	8581	138,500,001	140,600,000	gneg
4	q	31.21	8581	8733	140,600,001	145,900,000	gpos	25
4	q	31.22	8733	8851	145,900,001	147,500,000	gneg
4	q	31.23	8851	9004	147,500,001	150,200,000	gpos	25
4	q	31.3	9004	9207	150,200,001	154,600,000	gneg
4	q	32.1	9207	9545	154,600,001	160,800,000	gpos	100
4	q	32.2	9545	9681	160,800,001	163,600,000	gneg
4	q	32.3	9681	9985	163,600,001	169,200,000	gpos	100
4	q	33	9985	10087	169,200,001	171,000,000	gneg
4	q	34.1	10087	10341	171,000,001	175,400,000	gpos	75
4	q	34.2	10341	10408	175,400,001	176,600,000	gneg
4	q	34.3	10408	10628	176,600,001	182,300,000	gpos	100
4	q	35.1	10628	10967	182,300,001	186,200,000	gneg
4	q	35.2	10967	11170	186,200,001	190,214,555	gpos	25

References

1. "Search results - 4[CHR] AND "Homo sapiens"[Organism] AND ("has ccds"[Properties] AND alive[prop]) - Gene". NCBI. CCDS Release 20 for Homo sapiens. 2016-09-08. Retrieved 2017-05-28.
2. Tom Strachan; Andrew Read (2 April 2010). Human Molecular Genetics. Garland Science. p. 45. ISBN 978-1-136-84407-2.
3. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). Last update 2014-06-03. Retrieved 2017-04-26.
4. Chen LC, Liu MY, Hsiao YC, Choong WK, Wu HY, Hsu WL, Liao PC, Sung TY, Tsai SF, Yu JS, Chen YJ (2012) Decoding the disease-associated proteins encoded in the human chromosome 4. J Proteome Res
5. Pertea M, Salzberg SL (2010). "Between a chicken and a grape: estimating the number of human genes". Genome Biol. 11 (5): 206. doi:10.1186/gb-2010-11-5-206. PMC 2898077. PMID 20441615.
6. "Statistics & Downloads for chromosome 4". HUGO Gene Nomenclature Committee. 2017-05-12. Archived from the original on 2017-06-29. Retrieved 2017-05-19.
7. "Chromosome 4: Chromosome summary - Homo sapiens". Ensembl Release 88. 2017-03-29. Retrieved 2017-05-19.
8. "Human chromosome 4: entries, gene names and cross-references to MIM". UniProt. 2018-02-28. Retrieved 2018-03-16.
9. "Search results - 4[CHR] AND "Homo sapiens"[Organism] AND ("genetype protein coding"[Properties] AND alive[prop]) - Gene". NCBI. 2017-05-19. Retrieved 2017-05-20.
10. "Search results - 4[CHR] AND "Homo sapiens"[Organism] AND ( ("genetype miscrna"[Properties] OR "genetype ncrna"[Properties] OR "genetype rrna"[Properties] OR "genetype trna"[Properties] OR "genetype scrna"[Properties] OR "genetype snrna"[Properties] OR "genetype snorna"[Properties]) NOT "genetype protein coding"[Properties] AND alive[prop]) - Gene". NCBI. 2017-05-19. Retrieved 2017-05-20.
11. "Search results - 4[CHR] AND "Homo sapiens"[Organism] AND ("genetype pseudo"[Properties] AND alive[prop]) - Gene". NCBI. 2017-05-19. Retrieved 2017-05-20.
12. Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camaño P, Dauwerse JG, Snider L, Straasheijm KR, van Ommen GJ, Padberg GW, Miller DG, Tapscott SJ, Tawil R, Frants RR, van der Maarel SM (September 2010). "A unifying genetic model for facioscapulohumeral muscular dystrophy". Science. 329 (5999): 1650–3. Bibcode:2010Sci...329.1650L. doi:10.1126/science.1189044. PMC 4677822. PMID 20724583.
13. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (400 bphs, Assembly GRCh38.p3). Last update 2014-03-04. Retrieved 2017-04-26.
14. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (550 bphs, Assembly GRCh38.p3). Last update 2015-08-11. Retrieved 2017-04-26.
15. International Standing Committee on Human Cytogenetic Nomenclature (2013). ISCN 2013: An International System for Human Cytogenetic Nomenclature (2013). Karger Medical and Scientific Publishers. ISBN 978-3-318-02253-7.
16. Sethakulvichai, W.; Manitpornsut, S.; Wiboonrat, M.; Lilakiatsakun, W.; Assawamakin, A.; Tongsima, S. (2012). "Estimation of band level resolutions of human chromosome images". 2012 Ninth International Conference on Computer Science and Software Engineering (JCSSE). pp. 276–282. doi:10.1109/JCSSE.2012.6261965. ISBN 978-1-4673-1921-8. S2CID 16666470.
17. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). Last update 2014-06-03. Retrieved 2017-04-26.
18. "p": Short arm; "q": Long arm.
19. For cytogenetic banding nomenclature, see article locus.
20. These values (ISCN start/stop) are based on the length of bands/ideograms from the ISCN book, An International System for Human Cytogenetic Nomenclature (2013). Arbitrary unit.
21. gpos: Region which is positively stained by G banding, generally AT-rich and gene poor; gneg: Region which is negatively stained by G banding, generally CG-rich and gene rich; acen Centromere. var: Variable region; stalk: Stalk.

Further reading

• Goldfrank D, Schoenberger E, Gilbert F (2003). "Disease genes and chromosomes: disease maps of the human genome. Chromosome 4". Genet Test. 7 (4): 351–72. doi:10.1089/109065703322783752. PMID 15000816.

• Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, et al. (April 2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. Bibcode:2005Natur.434..724H. doi:10.1038/nature03466. PMID 15815621.

External links

• National Institutes of Health. "Chromosome 4". Genetics Home Reference. Archived from the original on August 3, 2004. Retrieved 2017-05-06.
• "Chromosome 4". Human Genome Project Information Archive 1990–2003. Retrieved 2017-05-06.