C4orf54

Summary

C4orf54 (chromosome 4 open reading frame 54, HGNC:27741) is a protein-coding gene on chromosome 4q23, encoding Uncharacterized protein C4orf54 (D6RIA3).

At a glance

• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_001354435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27741
Approved symbol	C4orf54
Name	chromosome 4 open reading frame 54
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	FOPV, LOC285556
Ensembl gene	ENSG00000248713
Ensembl biotype	protein_coding
OMIM	617881
Entrez	285556

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000511828

RefSeq mRNA: 1 — MANE Select: NM_001354435 NM_001354435

CCDS: CCDS87246

Canonical transcript exons

ENST00000511828 — 3 exons

Exon	Start	End
ENSE00002045944	99649231	99654679
ENSE00002057381	99636529	99641196
ENSE00003921811	99657495	99657828

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 99.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1355 / max 25.1868, expressed in 37 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53292	0.0575	20
53294	0.0364	13
53291	0.0232	11
53293	0.0184	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	99.02	gold quality
vastus lateralis	UBERON:0001379	98.90	gold quality
quadriceps femoris	UBERON:0001377	98.80	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.74	gold quality
deltoid	UBERON:0001476	98.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.49	gold quality
tibialis anterior	UBERON:0001385	97.09	gold quality
skeletal muscle tissue	UBERON:0001134	97.08	gold quality
body of tongue	UBERON:0011876	96.06	gold quality
muscle tissue	UBERON:0002385	89.88	gold quality
tongue	UBERON:0001723	88.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.89	gold quality
gastrocnemius	UBERON:0001388	85.55	gold quality
muscle of leg	UBERON:0001383	85.12	gold quality
heart right ventricle	UBERON:0002080	81.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.30	gold quality
superior surface of tongue	UBERON:0007371	76.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.86	silver quality
oviduct epithelium	UBERON:0004804	74.67	gold quality
myocardium	UBERON:0002349	73.78	silver quality
pharyngeal mucosa	UBERON:0000355	69.63	gold quality
left ventricle myocardium	UBERON:0006566	68.21	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.69	gold quality
buccal mucosa cell	CL:0002336	59.81	silver quality
cardiac atrium	UBERON:0002081	59.81	gold quality
cardiac ventricle	UBERON:0002082	59.63	gold quality
heart left ventricle	UBERON:0002084	59.37	gold quality
right atrium auricular region	UBERON:0006631	59.36	gold quality
renal medulla	UBERON:0000362	58.55	gold quality
oral cavity	UBERON:0000167	58.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.57

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C7H4orf54	ENSDARG00000098379
mus_musculus	1110002E22Rik	ENSMUSG00000090066
rattus_norvegicus	C2h4orf54	ENSRNOG00000063384

Protein

Protein identifiers

Uncharacterized protein C4orf54 — D6RIA3 (reviewed: D6RIA3)

Alternative names: Familial obliterative portal venopathy

All UniProt accessions (1): D6RIA3

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in muscle, heart, kidney and liver but barely detectable in lung, pancreas and brain. In liver veins, expressed in hepatic vein, extrahepatic portal vein and intrahepatic portal vein.

Disease relevance. Defects in C4orf54 may cause obliterative portal venopathy (OVP), a defect characterized by lesions of the intrahepatic branches of the portal vein that may lead to the occlusion or the obliteration of the small branches of the portal vein. Obliterative portal venopathy is currently thought to be responsible for many cases of portal hypertension in the absence of cirrhosis or obstruction of large portal or hepatic veins. Authors suggest a pathogenic role of FOPV mutations in some familial cases of OPV, with a pattern of autosomal dominant inheritance with incomplete penetrance and variable expressivity. Also, FOPV mutations may be involved in some non-familial cases.

RefSeq proteins (1): NP_001341364* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027838	DUF4585	Domain
IPR052303	CEFIP	Family

Pfam: PF15232

UniProt features (34 total): compositionally biased region 17, region of interest 10, modified residue 3, sequence variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-D6RIA3-F1	40.38	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 733, 1187, 1774

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, DARWICHE_PAPILLOMA_PROGRESSION_RISK, KASLER_HDAC7_TARGETS_1_UP, GSE11864_UNTREATED_VS_CSF1_IFNG_PAM3CYS_IN_MAC_DN, DESCARTES_MAIN_FETAL_SKELETAL_MUSCLE_CELLS, MZF1_TARGET_GENES, GSE2197_CPG_DNA_VS_UNTREATED_IN_DC_UP, WP_GENETIC_CAUSES_OF_PORTOSINUSOIDAL_VASCULAR_DISEASE, GSE26495_PD1HIGH_VS_PD1LOW_CD8_TCELL_DN, ZHANG_FH_DEFICIENT_RCC_TUMOR_VS_NORMAL_DN, GSE30962_PRIMARY_VS_SECONDARY_CHRONIC_LCMV_INF_CD8_TCELL_DN, GSE2124_CTRL_VS_LYMPHOTOXIN_BETA_TREATED_MLN_DN, GSE2405_HEAT_KILLED_LYSATE_VS_LIVE_A_PHAGOCYTOPHILUM_STIM_NEUTROPHIL_24H_DN, GSE2405_0H_VS_12H_A_PHAGOCYTOPHILUM_STIM_NEUTROPHIL_DN, ZHANG_BREAST_CANCER_PROGENITORS_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C4orf54	EEF1G	P26641	134
C4orf54	TERT	O14746	115
C4orf54	DICER1	Q9UPY3	102
C4orf54	ALG2	Q9H553	97
C4orf54	TEP1	Q99973	93
C4orf54	TNN	Q9UQP3	92
C4orf54	TNC	P24821	92
C4orf54	TNR	Q92752	92
C4orf54	NOC3L	Q8WTT2	92
C4orf54	ELP4	Q96EB1	92
C4orf54	ELP3	Q9H9T3	90
C4orf54	ELP1	O95163	90
C4orf54	RPL23A	P29316	90
C4orf54	EIF6	P56537	89
C4orf54	TEX10	Q9NXF1	89

IntAct

2 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (4): LOC285556 (Synthetic Lethality), LOC285556 (Affinity Capture-MS), LOC285556 (Cross-Linking-MS (XL-MS)), LOC285556 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K1J5A5, A0A2K1JJ00, A0MS83, A2AWL7, A2BIL8, A6H619, A9ZPC9, D3Z3C6, D6RIA3, E9PSU6, P09272, P09309, P09310, P46012, P46934, P55200, Q03164, Q0VAV2, Q1LY77, Q1RMQ5, Q4JQW6, Q4V7J0, Q5RD08, Q5SPL2, Q62417, Q63625, Q6DFV3, Q6NRV8, Q6NZN1, Q6P6I6, Q703I1, Q7TQC7, Q80WR5, Q865B7, Q8AZM1, Q8IWI9, Q8NG27, Q8QVM1, Q8V7G4, Q93ZL5

Diamond homologs: D6RIA3, E0CYV9, Q711Q0, D3Z1D3, M0RD54

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	15
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

251 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99641064:CACA:C	donor_gain	1.0000
4:99641072:G:C	donor_gain	0.9900
4:99641143:A:AC	donor_gain	0.9800
4:99641063:A:AC	donor_gain	0.9700
4:99641064:C:CC	donor_gain	0.9700
4:99641064:CA:C	donor_gain	0.9700
4:99650984:ATCTT:A	acceptor_gain	0.9700
4:99643636:CAAA:C	acceptor_gain	0.9400
4:99650985:TCTTG:T	acceptor_gain	0.9400
4:99641062:TACAC:T	donor_gain	0.9200
4:99641063:ACACA:A	donor_gain	0.9200
4:99641064:CACAC:C	donor_gain	0.9200
4:99649230:CCAG:C	donor_gain	0.9200
4:99649225:ACTT:A	donor_loss	0.9100
4:99649226:CTTA:C	donor_loss	0.9100
4:99649227:TTACC:T	donor_loss	0.9100
4:99649228:T:TG	donor_loss	0.9100
4:99649229:A:AC	donor_gain	0.9100
4:99649229:A:T	donor_loss	0.9100
4:99649230:C:CC	donor_gain	0.9100
4:99649230:C:CG	donor_loss	0.9100
4:99649230:CCA:C	donor_gain	0.9000
4:99641068:CTTAG:C	donor_gain	0.8900
4:99641137:A:AC	donor_gain	0.8900
4:99649224:CACT:C	donor_loss	0.8900
4:99650972:GCCTT:G	acceptor_gain	0.8700
4:99650983:AATCT:A	acceptor_gain	0.8700
4:99641062:TAC:T	donor_gain	0.8500
4:99641063:ACA:A	donor_gain	0.8500
4:99641064:CAC:C	donor_gain	0.8500

AlphaMissense

11647 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99650826:A:G	W1275R	1.000
4:99650826:A:T	W1275R	1.000
4:99652772:A:G	L626P	1.000
4:99649286:A:G	F1788S	0.999
4:99649811:A:G	L1613P	0.999
4:99650824:C:A	W1275C	0.999
4:99650824:C:G	W1275C	0.999
4:99650870:G:T	A1260D	0.999
4:99650871:C:G	A1260P	0.999
4:99650879:A:G	L1257P	0.999
4:99652493:A:G	F719S	0.999
4:99652748:A:G	L634P	0.999
4:99652756:G:C	F631L	0.999
4:99652756:G:T	F631L	0.999
4:99652757:A:G	F631S	0.999
4:99652758:A:G	F631L	0.999
4:99649285:A:C	F1788L	0.998
4:99649285:A:T	F1788L	0.998
4:99649287:A:G	F1788L	0.998
4:99649785:A:C	Y1622D	0.998
4:99650820:G:T	R1277S	0.998
4:99650825:C:G	W1275S	0.998
4:99651038:G:T	A1204D	0.998
4:99651317:A:G	L1111P	0.998
4:99651330:C:G	D1107H	0.998
4:99651389:A:G	F1087S	0.998
4:99651557:A:G	I1031T	0.998
4:99652202:A:T	V816D	0.998
4:99652211:A:G	L813P	0.998
4:99652750:G:C	S633R	0.998

dbSNP variants (sampled 300 via entrez): RS1000059977 (4:99656506 T>A,C), RS1000189030 (4:99639170 C>A,T), RS1000209130 (4:99651823 A>G), RS1000443770 (4:99654801 T>C), RS1000612559 (4:99658193 C>G), RS1000662925 (4:99655790 A>T), RS1000668323 (4:99646183 G>T), RS1000784951 (4:99652389 G>T), RS1000944835 (4:99652152 C>T), RS1000945999 (4:99644293 A>T), RS1001061807 (4:99657656 A>C), RS1001226457 (4:99636590 G>A,T), RS1001250125 (4:99650559 T>C), RS1001373786 (4:99651177 C>G,T), RS1001453854 (4:99657108 A>G)

Disease associations

OMIM: gene MIM:617881 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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