C4orf50

Summary

C4orf50 (chromosome 4 open reading frame 50, HGNC:33766) is a protein-coding gene on chromosome 4p16.2-p16.1, encoding Uncharacterized protein C4orf50 (Q6ZRC1).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 12 total — 2 pathogenic
• MANE Select transcript: NM_001364689

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33766
Approved symbol	C4orf50
Name	chromosome 4 open reading frame 50
Location	4p16.2-p16.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46481
Ensembl gene	ENSG00000181215
Ensembl biotype	protein_coding
Entrez	389197

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000531445, ENST00000639345, ENST00000711657

RefSeq mRNA: 2 — MANE Select: NM_001364689 NM_001364689, NM_001364690

CCDS: CCDS93473

Canonical transcript exons

ENST00000711657 — 12 exons

Exon	Start	End
ENSE00001364444	5975899	5975955
ENSE00001374945	5973659	5973841
ENSE00001375947	5980174	5980338
ENSE00001379628	5967414	5967462
ENSE00001390561	5965024	5965145
ENSE00002190921	5988347	5990824
ENSE00003792539	6011830	6011968
ENSE00003792726	5992803	5992930
ENSE00003795534	6007996	6008532
ENSE00003799198	5994347	5994476
ENSE00004016324	5959375	5959626
ENSE00004016325	6018145	6018431

Expression profiles

Bgee: expression breadth broad, 49 present calls, max score 78.83.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0134 / max 158.6347, expressed in 375 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51233	4.0134	375

Top tissues by expression

119 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	78.83	gold quality
superior frontal gyrus	UBERON:0002661	77.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.34	silver quality
putamen	UBERON:0001874	74.34	gold quality
prefrontal cortex	UBERON:0000451	74.16	gold quality
caudate nucleus	UBERON:0001873	73.87	gold quality
frontal cortex	UBERON:0001870	73.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.32	gold quality
cerebral cortex	UBERON:0000956	71.22	gold quality
right frontal lobe	UBERON:0002810	70.80	gold quality
anterior cingulate cortex	UBERON:0009835	70.57	gold quality
primary visual cortex	UBERON:0002436	70.23	gold quality
cortical plate	UBERON:0005343	69.14	gold quality
Ammon’s horn	UBERON:0001954	68.11	gold quality
temporal lobe	UBERON:0001871	67.67	gold quality
amygdala	UBERON:0001876	67.51	gold quality
hypothalamus	UBERON:0001898	66.90	gold quality
brain	UBERON:0000955	65.19	gold quality
substantia nigra	UBERON:0002038	58.95	gold quality
granulocyte	CL:0000094	58.46	gold quality
corpus callosum	UBERON:0002336	57.32	gold quality
colonic epithelium	UBERON:0000397	57.10	gold quality
bone marrow cell	CL:0002092	54.02	gold quality
ventricular zone	UBERON:0003053	53.23	gold quality
islet of Langerhans	UBERON:0000006	49.92	gold quality
bone marrow	UBERON:0002371	48.54	gold quality
pituitary gland	UBERON:0000007	46.82	gold quality
sural nerve	UBERON:0015488	45.17	gold quality
lymph node	UBERON:0000029	44.84	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.86

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm1043	ENSMUSG00000117286
rattus_norvegicus	C14h4orf50	ENSRNOG00000038427

Protein

Protein identifiers

Uncharacterized protein C4orf50 — Q6ZRC1 (reviewed: Q6ZRC1)

All UniProt accessions (2): A0A1W2PRI9, Q6ZRC1

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (2): NP_001351618, NP_001351619 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032771	DUF4527	Family

Pfam: PF15030

UniProt features (19 total): region of interest 7, compositionally biased region 4, sequence variant 4, coiled-coil region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZRC1-F1	55.65	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 9 (showing top): chr4p16, MARTENS_TRETINOIN_RESPONSE_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GATA1_05, ZNF10_TARGET_GENES, DESCARTES_MAIN_FETAL_THYMIC_EPITHELIAL_CELLS, DESCARTES_FETAL_EYE_GANGLION_CELLS, DESCARTES_FETAL_INTESTINE_ENS_NEURONS, ZNF134_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

52 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C4orf50	H6PD	O95479	205
C4orf50	CLCF1	Q9UBD9	180
C4orf50	OTOP1	Q7RTM1	156
C4orf50	RAB30	Q15771	155
C4orf50	NNT	Q13423	128
C4orf50	K7N7A8	K7N7A8	128
C4orf50	SERINC4	A6NH21	48
C4orf50	TACC2	O95359	48
C4orf50	LY9	Q9HBG7	0
C4orf50	LRRC53	A6NM62	0
C4orf50	PRDM9	Q9NQV7	0
C4orf50	TNFRSF10D	Q9UBN6	0
C4orf50	ADGRE1	Q14246	0
C4orf50	OR2AJ1	Q8NGZ0	0
C4orf50	KLRG2	A4D1S0	0
C4orf50	MARCHF5	Q9NX47	0
C4orf50	OR51I1	Q9H343	0
C4orf50	NHSL3	Q9P206	0
C4orf50	FASTKD2	Q9NYY8	0
C4orf50	CD44	P16070	0
C4orf50	SAMD1	Q6SPF0	0
C4orf50	PERCC1	A0A1W2PR82	0

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NDEL1	C4orf50	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A096LP49, A0A1B0GVZ6, A2VE02, A5D7I0, A6NDZ8, A6NE82, A6NGG8, A6NJ08, A6NJI1, A6QP24, A7YY35, A8MYA2, O94850, P50617, Q0P5M0, Q2KIL8, Q2KIS6, Q3SY00, Q3ZBU3, Q497N6, Q4R736, Q5BMD4, Q5JTZ5, Q5M844, Q5VZ46, Q5XIK6, Q66MI6, Q6AXP4, Q6PAC4, Q6ZRC1, Q7L2K0, Q7Z591, Q80TS7, Q80VW7, Q8BFY7, Q8BHW6, Q8IXW0, Q8IYS4, Q8IYX3, Q8N4L8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

12 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	4
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2424447	NC_000004.11:g.(?4861627)(6304195_?)del	Pathogenic
816497	GRCh37/hg19 4p16.3-15.2(chr4:49450-24280482)x1	Pathogenic

SpliceAI

3968 predictions. Top by Δscore:

Variant	Effect	Δscore
4:5973658:CCT:C	donor_gain	1.0000
4:5973669:C:CA	donor_gain	1.0000
4:5973698:AG:A	donor_gain	1.0000
4:5973698:AGC:A	donor_gain	1.0000
4:5973699:G:C	donor_gain	1.0000
4:5980166:T:TA	donor_gain	1.0000
4:5980167:C:A	donor_gain	1.0000
4:5980190:T:TA	donor_gain	1.0000
4:6060419:CTCA:C	donor_loss	1.0000
4:6060420:TCAC:T	donor_loss	1.0000
4:6060421:CACC:C	donor_loss	1.0000
4:6060423:C:T	donor_loss	1.0000
4:6060503:CGAGT:C	acceptor_gain	1.0000
4:6060504:GAGT:G	acceptor_gain	1.0000
4:6060506:GT:G	acceptor_gain	1.0000
4:6060506:GTC:G	acceptor_loss	1.0000
4:6060507:TCTGG:T	acceptor_loss	1.0000
4:6060508:C:CC	acceptor_gain	1.0000
4:6060508:C:T	acceptor_loss	1.0000
4:6062310:AC:A	donor_gain	1.0000
4:6062311:CC:C	donor_gain	1.0000
4:6062439:GC:G	acceptor_gain	1.0000
4:6062440:CC:C	acceptor_gain	1.0000
4:6062441:C:CC	acceptor_gain	1.0000
4:6062444:CACA:C	acceptor_gain	1.0000
4:6062446:C:CT	acceptor_gain	1.0000
4:6062447:A:AC	acceptor_gain	1.0000
4:6062447:A:C	acceptor_gain	1.0000
4:6062450:A:AC	acceptor_gain	1.0000
4:6062450:A:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000289 (4:5918678 C>T), RS1000010262 (4:5951775 G>A,C), RS10000138 (4:5949970 C>A,T), RS1000028695 (4:6016751 A>C), RS1000071891 (4:5954375 C>T), RS1000110236 (4:5996761 G>C), RS1000140446 (4:5917706 T>A), RS1000188189 (4:5978435 G>C), RS1000191624 (4:6018636 T>C), RS1000197477 (4:5946471 C>G), RS10002154 (4:5931726 C>T), RS1000219210 (4:5978788 C>T), RS1000241567 (4:6012010 T>G), RS1000244751 (4:5945743 A>G), RS1000247628 (4:5951044 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:189500

GenCC curated gene-disease

Mondo (1): tooth and nail syndrome (MONDO:0008582)

Orphanet (1): Hypodontia-dysplasia of nails syndrome (Orphanet:2228)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002040_6	Blood trace element (Zn levels)	3.000000e-06
GCST012051_4	Systolic blood pressure	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536736	Witkop syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
potassium chromate(VI)	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.