C2orf74

Summary

C2orf74 (chromosome 2 open reading frame 74, HGNC:34439) is a protein-coding gene on chromosome 2p15, encoding Uncharacterized protein C2orf74 (A8MZ97).

Predicted to be located in membrane.

Source: NCBI Gene 339804 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 16 total — 2 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_001143959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34439
Approved symbol	C2orf74
Name	chromosome 2 open reading frame 74
Location	2p15
Locus type	gene with protein product
Status	Approved
Aliases	LOC339804
Ensembl gene	ENSG00000237651
Ensembl biotype	protein_coding
Entrez	339804

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000398622, ENST00000426997, ENST00000432605, ENST00000464909, ENST00000488469, ENST00000489686

RefSeq mRNA: 6 — MANE Select: NM_001143959 NM_001143959, NM_001143960, NM_001316317, NM_001367069, NM_001367070, NM_001367071

CCDS: CCDS46297, CCDS46298

Canonical transcript exons

ENST00000432605 — 5 exons

Exon	Start	End
ENSE00001533957	61164354	61164828
ENSE00001878215	61162416	61162609
ENSE00003495042	61163052	61163232
ENSE00003597378	61162842	61162955
ENSE00003913910	61162188	61162320

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1042 / max 875.5705, expressed in 1688 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20472	18.3366	1683
20473	0.7591	479
202205	0.0050	3
202204	0.0035	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	96.64	gold quality
amygdala	UBERON:0001876	96.53	gold quality
hypothalamus	UBERON:0001898	96.52	gold quality
substantia nigra	UBERON:0002038	96.50	gold quality
putamen	UBERON:0001874	96.38	gold quality
temporal lobe	UBERON:0001871	96.35	gold quality
caudate nucleus	UBERON:0001873	96.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.97	gold quality
Ammon’s horn	UBERON:0001954	95.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.70	gold quality
anterior cingulate cortex	UBERON:0009835	95.61	gold quality
cerebral cortex	UBERON:0000956	95.33	gold quality
left testis	UBERON:0004533	95.31	gold quality
prefrontal cortex	UBERON:0000451	95.21	gold quality
frontal cortex	UBERON:0001870	95.07	gold quality
superior frontal gyrus	UBERON:0002661	95.05	gold quality
right frontal lobe	UBERON:0002810	94.94	gold quality
right testis	UBERON:0004534	94.77	gold quality
brain	UBERON:0000955	94.76	gold quality
testis	UBERON:0000473	94.75	gold quality
primary visual cortex	UBERON:0002436	94.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.86	gold quality
right atrium auricular region	UBERON:0006631	93.25	gold quality
apex of heart	UBERON:0002098	93.00	gold quality
heart left ventricle	UBERON:0002084	92.77	gold quality
pituitary gland	UBERON:0000007	92.60	gold quality
heart	UBERON:0000948	92.51	gold quality
islet of Langerhans	UBERON:0000006	91.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.87	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.40
E-GEOD-124858	no	186.69
E-GEOD-83139	no	2.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting C2orf74, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-6869-5P	97.17	67.06	634
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-4680-5P	96.43	67.15	893
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-3130-3P	94.98	66.97	574

Literature-anchored findings (GeneRIF, showing 1)

• Frameshift variant in MITF gene in a large family with Waardenburg syndrome type II and a co-segregation of a C2orf74 variant. (PMID:33571247)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	1700093K21Rik	ENSMUSG00000020286
rattus_norvegicus	C14h2orf74	ENSRNOG00000051590

Protein

Protein identifiers

Uncharacterized protein C2orf74 — A8MZ97 (reviewed: A8MZ97)

All UniProt accessions (5): A8MZ97, A0A087WXS6, A0A087X1C3, C9JBF1, F8VY72

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (6): NP_001137431, NP_001137432, NP_001303246, NP_001353998, NP_001353999, NP_001354000 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027813	DUF4642	Family

Pfam: PF15484

UniProt features (4 total): chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MZ97-F1	58.68	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN, SRSF9_TARGET_GENES, LET_7C_3P, MIR507, MIR557, GSE10856_CTRL_VS_TNFRSF6B_IN_MACROPHAGE_DN, MIR6869_5P, GAO_LARGE_INTESTINE_ADULT_CE_OLFM4HIGH_STEM_CELL, HBZ_TARGET_GENES, ZNF133_TARGET_GENES, THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_7DY_UP, HOEK_MONOCYTE_2011_2012_TIV_ADULT_1DY_DN, GSE17721_0.5H_VS_8H_POLYIC_BMDC_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

152 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2orf74	SANBR	Q6NSI8	668
C2orf74	SIRPD	Q9H106	570
C2orf74	NPIPB8	E9PQR5	529
C2orf74	FAM162B	Q5T6X4	506
C2orf74	MINDY4	Q4G0A6	447
C2orf74	PUS10	Q3MIT2	431
C2orf74	FAM161A	Q3B820	419
C2orf74	XRRA1	Q6P2D8	377
C2orf74	HRCT1	Q6UXD1	371
C2orf74	TMEM71	Q6P5X7	370
C2orf74	TMEM243	Q9BU79	369
C2orf74	INMT	O95050	357
C2orf74	SIRPB1	O00241	351
C2orf74	PLA2G15	Q8NCC3	349
C2orf74	ZNF512	Q96ME7	339

IntAct

5 interactions, top by confidence:

A	B	Type	Score
C2orf74	SMAGP	psi-mi:“MI:0915”(physical association)	0.560
C2orf74	POT1	psi-mi:“MI:0915”(physical association)	0.370
SMAGP	C2orf74	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): C2orf74 (Two-hybrid), C2orf74 (Affinity Capture-MS), C2orf74 (Affinity Capture-MS), POT1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GVT2, A0JNM1, A2APA5, A6H754, A6NLX4, A6PWV3, A7MB05, A8MZ97, O88472, P02725, P06740, P14221, P19103, Q02223, Q0VFL4, Q13522, Q1RMT9, Q28CW2, Q28HY7, Q2KIK3, Q2TBN9, Q498C7, Q56A20, Q5RA87, Q5RBQ2, Q5RCS3, Q5XIC3, Q60664, Q63HN8, Q6DJE5, Q6UWV7, Q6XQ84, Q7L3B6, Q7SXB3, Q7TMJ8, Q80WK2, Q810S2, Q86UW2, Q8NEA5, Q8WMS3

Diamond homologs: A8MZ97, Q810S2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1807687	GRCh37/hg19 2p16.1-15(chr2:61215497-61714418)x1	Pathogenic
1807738	GRCh37/hg19 2p15(chr2:61379352-61928100)x1	Pathogenic
395613	GRCh37/hg19 2p15(chr2:61335464-61757267)x1	Likely pathogenic
523277	GRCh37/hg19 2p16.1-15(chr2:60308869-62368583)	Likely pathogenic

SpliceAI

274 predictions. Top by Δscore:

Variant	Effect	Δscore
2:61162971:G:GT	donor_gain	1.0000
2:61164349:TGCA:T	acceptor_loss	1.0000
2:61164350:GCA:G	acceptor_loss	1.0000
2:61164352:A:AG	acceptor_gain	1.0000
2:61164352:AG:A	acceptor_gain	1.0000
2:61164352:AGG:A	acceptor_loss	1.0000
2:61164352:AGGAT:A	acceptor_gain	1.0000
2:61164353:G:GA	acceptor_gain	1.0000
2:61164353:GG:G	acceptor_gain	1.0000
2:61164353:GGAT:G	acceptor_gain	1.0000
2:61164353:GGATG:G	acceptor_gain	1.0000
2:61163223:TCAAG:T	donor_gain	0.9900
2:61163230:G:GT	donor_gain	0.9900
2:61164342:A:AG	acceptor_gain	0.9900
2:61164353:GGA:G	acceptor_gain	0.9900
2:61163230:GAG:G	donor_gain	0.9800
2:61163228:AAGAG:A	donor_loss	0.9700
2:61163229:AGAGG:A	donor_loss	0.9700
2:61163230:GAGGT:G	donor_loss	0.9700
2:61163231:AGGTG:A	donor_loss	0.9700
2:61163232:GG:G	donor_loss	0.9700
2:61163233:G:A	donor_loss	0.9700
2:61163234:T:C	donor_loss	0.9700
2:61164343:T:G	acceptor_gain	0.9700
2:61162592:G:GA	donor_gain	0.9600
2:61162928:TGAC:T	donor_gain	0.9600
2:61164349:T:TA	acceptor_gain	0.9600
2:61163122:G:GT	donor_gain	0.9400
2:61162591:T:TA	donor_gain	0.9300
2:61163046:TTCTA:T	acceptor_loss	0.9200

AlphaMissense

1285 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:61164441:T:C	F167L	0.997
2:61164443:T:A	F167L	0.997
2:61164443:T:G	F167L	0.997
2:61164442:T:G	F167C	0.991
2:61163099:T:C	I93T	0.988
2:61164442:T:C	F167S	0.987
2:61162563:T:C	C24R	0.986
2:61164431:A:C	K163N	0.983
2:61164431:A:T	K163N	0.983
2:61164430:A:T	K163I	0.976
2:61164460:T:A	V173D	0.975
2:61162572:T:C	C27R	0.972
2:61163099:T:G	I93S	0.965
2:61164451:A:T	E170V	0.965
2:61162596:T:C	F35L	0.963
2:61162598:T:A	F35L	0.963
2:61162598:T:G	F35L	0.963
2:61164444:T:C	S168P	0.963
2:61164457:T:A	I172N	0.963
2:61164472:G:T	G177V	0.962
2:61164515:A:C	K191N	0.961
2:61164515:A:T	K191N	0.961
2:61164521:G:C	R193S	0.961
2:61164521:G:T	R193S	0.961
2:61163105:T:A	V95D	0.959
2:61163112:A:C	R97S	0.959
2:61163112:A:T	R97S	0.959
2:61164457:T:G	I172S	0.958
2:61164453:G:C	V171L	0.957
2:61164453:G:T	V171L	0.957

dbSNP variants (sampled 300 via entrez): RS1000036430 (2:61159570 A>C,G), RS1000131658 (2:61163810 C>G,T), RS1000145871 (2:61158088 C>T), RS1000198846 (2:61144622 G>A), RS1000240948 (2:61158221 T>A,C), RS1000356007 (2:61152228 T>G), RS1000550171 (2:61147466 C>G,T), RS1000648464 (2:61147695 T>C), RS1000651722 (2:61149246 T>C), RS1000893510 (2:61152402 G>A), RS1000954693 (2:61155066 A>G), RS1000990414 (2:61160747 C>T), RS1001098845 (2:61162902 T>C,G), RS1001149622 (2:61154832 A>G), RS1001199176 (2:61144283 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:614883

GenCC curated gene-disease

Mondo (1): peroxisome biogenesis disorder 11A (Zellweger) (MONDO:0013949)

Orphanet (1): Zellweger syndrome (Orphanet:912)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000879_48	Crohn’s disease	7.000000e-09
GCST001438_15	Crohn’s disease	5.000000e-09
GCST001725_44	Inflammatory bowel disease	9.000000e-32
GCST90002386_248	High light scatter reticulocyte percentage of red cells	2.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression, increases expression	2
arsenite	affects binding, increases reaction	1
jinfukang	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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