C22orf31

Summary

C22orf31 (chromosome 22 open reading frame 31, HGNC:26931) is a protein-coding gene on chromosome 22q12.1, encoding Uncharacterized protein C22orf31 (O95567).

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 14 total — 1 pathogenic
• MANE Select transcript: NM_015370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26931
Approved symbol	C22orf31
Name	chromosome 22 open reading frame 31
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	HS747E2A, bK747E2.1
Ensembl gene	ENSG00000100249
Ensembl biotype	protein_coding
Entrez	25770

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000216071

RefSeq mRNA: 2 — MANE Select: NM_015370 NM_001386866, NM_015370

CCDS: CCDS13848

Canonical transcript exons

ENST00000216071 — 3 exons

Exon	Start	End
ENSE00000651998	29060415	29060843
ENSE00000879699	29058672	29059182
ENSE00001048193	29061790	29061831

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 96.01.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.01	gold quality
pancreatic ductal cell	CL:0002079	83.30	silver quality
sperm	CL:0000019	79.36	gold quality
male germ cell	CL:0000015	78.12	gold quality
right testis	UBERON:0004534	75.63	gold quality
left testis	UBERON:0004533	75.01	gold quality
testis	UBERON:0000473	73.14	gold quality
buccal mucosa cell	CL:0002336	71.51	silver quality
triceps brachii	UBERON:0001509	68.81	gold quality
gluteal muscle	UBERON:0002000	67.84	gold quality
epithelial cell of pancreas	CL:0000083	67.83	silver quality
putamen	UBERON:0001874	66.25	gold quality
endometrium epithelium	UBERON:0004811	65.26	gold quality
lateral globus pallidus	UBERON:0002476	64.83	silver quality
tendon of biceps brachii	UBERON:0008188	64.66	gold quality
hair follicle	UBERON:0002073	64.23	gold quality
caudate nucleus	UBERON:0001873	64.15	gold quality
parotid gland	UBERON:0001831	63.11	gold quality
deltoid	UBERON:0001476	62.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.06	gold quality
heart right ventricle	UBERON:0002080	61.63	gold quality
cranial nerve II	UBERON:0000941	61.38	silver quality
epithelium of nasopharynx	UBERON:0001951	61.07	gold quality
biceps brachii	UBERON:0001507	60.88	gold quality
paraflocculus	UBERON:0005351	60.78	gold quality
nucleus accumbens	UBERON:0001882	60.63	gold quality
frontal pole	UBERON:0002795	60.22	gold quality
middle frontal gyrus	UBERON:0002702	60.08	gold quality
olfactory bulb	UBERON:0002264	59.91	gold quality
pigmented layer of retina	UBERON:0001782	59.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.62

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Uncharacterized protein C22orf31 — O95567 (reviewed: O95567)

All UniProt accessions (1): O95567

RefSeq proteins (2): NP_001373795, NP_056185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028970	DUF4662	Family

Pfam: PF15578

UniProt features (8 total): compositionally biased region 3, region of interest 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95567-F1	57.02	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): GCANCTGNY_MYOD_Q6, CHX10_01, MODULE_99, TGANTCA_AP1_C, TGACATY_UNKNOWN, GATA1_04, LYF1_01, HAND1E47_01, MODULE_48, MODULE_95, TGGAAA_NFAT_Q4_01, TAATTA_CHX10_01, WGGAATGY_TEF1_Q6, E4BP4_01, YTAAYNGCT_UNKNOWN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

90 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C22orf31	TEDC1	Q86SX3	541
C22orf31	ESYT3	A0FGR9	497
C22orf31	TMED10	P49755	477
C22orf31	TP53I13	Q8NBR0	476
C22orf31	LONRF3	Q496Y0	447
C22orf31	KRT33B	Q14525	446
C22orf31	KLHL20	Q9Y2M5	409
C22orf31	LPCAT2	Q7L5N7	397
C22orf31	NR1H2	P55055	385
C22orf31	SYVN1	Q86TM6	378
C22orf31	C2orf78	A6NCI8	377
C22orf31	ACTBL2	Q562R1	369
C22orf31	METRNL	Q641Q3	306
C22orf31	TBCEL	Q5QJ74	297
C22orf31	KIF17	Q9P2E2	290

IntAct

4 interactions, top by confidence:

A	B	Type	Score
C22orf31	HDAC2	psi-mi:“MI:0914”(association)	0.530
ECE1	C22orf31	psi-mi:“MI:0915”(physical association)	0.370
C22orf31	HDAC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): HDAC1 (Affinity Capture-MS), LACRT (Affinity Capture-MS), LACRT (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), C22orf31 (Biochemical Activity), HDAC2 (Affinity Capture-MS), LACRT (Affinity Capture-MS), MBD2 (Cross-Linking-MS (XL-MS)), SMC6 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GVR7, A0PJW8, A2BYT2, A5FRX9, B8G1X0, C1DKL7, G3UWD5, O42659, O62953, O95567, O98453, P05899, P11690, P11794, P19718, P20920, P27975, P32544, P33482, P39971, P52776, P54446, P69516, P69517, P86209, Q02781, Q0ABH1, Q1X6Y0, Q3AMN4, Q3J8R8, Q3K5Z2, Q3MFB7, Q3ZZM0, Q537H7, Q57P89, Q5I162, Q5PHY6, Q6AY31, Q75003, Q7CQJ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
832563	NC_000022.10:g.(?29083885)(29621477_?)del	Pathogenic

SpliceAI

528 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29059181:CT:C	acceptor_gain	0.9900
22:29060442:ATGC:A	donor_gain	0.9900
22:29059188:C:CT	acceptor_gain	0.9700
22:29060486:T:TA	donor_gain	0.9700
22:29060844:C:CC	acceptor_gain	0.9700
22:29061133:T:TA	donor_gain	0.9700
22:29060427:T:TA	donor_gain	0.9600
22:29060438:T:TA	donor_gain	0.9600
22:29060659:T:TA	donor_gain	0.9600
22:29060842:TG:T	acceptor_gain	0.9600
22:29059183:C:CC	acceptor_gain	0.9500
22:29059189:A:T	acceptor_gain	0.9500
22:29060660:C:A	donor_gain	0.9500
22:29060839:GGGTG:G	acceptor_gain	0.9500
22:29060841:GTG:G	acceptor_gain	0.9500
22:29060705:TTGC:T	donor_gain	0.9400
22:29060840:GGTGC:G	acceptor_loss	0.9400
22:29060842:TGCTA:T	acceptor_loss	0.9400
22:29060843:GC:G	acceptor_loss	0.9400
22:29060844:CT:C	acceptor_loss	0.9400
22:29060845:T:A	acceptor_loss	0.9400
22:29060654:CAA:C	donor_gain	0.9300
22:29060840:GGTG:G	acceptor_gain	0.9300
22:29061137:G:A	donor_gain	0.9000
22:29060850:T:TC	acceptor_gain	0.8900
22:29060850:T:C	acceptor_gain	0.8600
22:29060988:T:A	donor_gain	0.8600
22:29059188:C:T	acceptor_gain	0.8500
22:29060416:T:TA	donor_gain	0.8500
22:29060460:G:A	donor_gain	0.8300

AlphaMissense

1884 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:29058883:T:A	K244N	0.987
22:29058883:T:G	K244N	0.987
22:29058884:T:A	K244I	0.984
22:29060663:A:G	W62R	0.960
22:29060663:A:T	W62R	0.960
22:29060661:C:A	W62C	0.956
22:29060661:C:G	W62C	0.956
22:29058896:C:T	G240D	0.947
22:29058885:T:C	K244E	0.940
22:29058896:C:A	G240V	0.939
22:29058884:T:G	K244T	0.938
22:29059001:A:G	I205T	0.937
22:29058966:A:C	Y217D	0.936
22:29058887:A:T	I243N	0.931
22:29058907:G:C	S236R	0.930
22:29058907:G:T	S236R	0.930
22:29058909:T:G	S236R	0.930
22:29059001:A:T	I205N	0.924
22:29058978:A:C	Y213D	0.920
22:29059001:A:C	I205S	0.918
22:29058997:A:C	H206Q	0.913
22:29058997:A:T	H206Q	0.913
22:29058897:C:G	G240R	0.911
22:29058887:A:C	I243S	0.909
22:29058912:A:G	Y235H	0.904
22:29058999:G:C	H206D	0.902
22:29058992:A:G	L208P	0.901
22:29060613:C:A	K78N	0.895
22:29060613:C:G	K78N	0.895
22:29058867:C:G	A250P	0.893

dbSNP variants (sampled 300 via entrez): RS1000069822 (22:29064907 G>A), RS1000934495 (22:29064930 T>C), RS1000983241 (22:29064645 C>A), RS1001102414 (22:29063296 G>A,T), RS1001239381 (22:29072819 G>C), RS1001286126 (22:29070848 G>A), RS1001526736 (22:29059368 A>G), RS1001630944 (22:29060232 A>G), RS1001703971 (22:29066378 G>A), RS1001808727 (22:29065547 C>T), RS1002079857 (22:29059790 A>C,G), RS1002291589 (22:29071256 G>C), RS1002392117 (22:29064582 C>T), RS1002624883 (22:29071546 G>A,C), RS1002950566 (22:29074907 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:114480

GenCC curated gene-disease

Mondo (1): hereditary breast carcinoma (MONDO:0016419)

Orphanet (1): Hereditary breast cancer (Orphanet:227535)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002553_2	Pancreatic cancer	1.000000e-08
GCST008395_14	End-stage kidney disease	2.000000e-07
GCST010658_22	High density lipoprotein cholesterol levels	7.000000e-08
GCST010662_18	Systolic blood pressure	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006335	systolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562840	Breast Cancer, Familial (supp.)

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
butyraldehyde	decreases expression	1
coumarin	decreases phosphorylation	1
pentanal	decreases expression	1
clothianidin	decreases expression	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00040222	Not specified	COMPLETED	Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer
NCT02557776	Not specified	COMPLETED	Written Genetic Counseling and Mutation Analysis of BRCA1 and BRCA2 to Patients With Breast Cancer
NCT03495544	Not specified	UNKNOWN	Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
NCT03959267	Not specified	COMPLETED	Testing a Culturally Adapted Telephone Genetic Counseling Intervention
NCT04058418	Not specified	COMPLETED	Specialist Recommendation on FBC (Familial Breast Cancer) Chemoprevention Prescribing
NCT04125914	Not specified	ACTIVE_NOT_RECRUITING	Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families
NCT04169542	Not specified	RECRUITING	Impact of COVID-19 Pandemic on Out-of-Pocket Costs, Lost Wages, and Unemployment in Patients With Breast Cancer Undergoing Breast Surgery
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT07292246	Not specified	RECRUITING	A Prospective CohorT Study of HandX - Assisted ENdoscopic MAstectomy: Feasibility and Safety (ATHENA I Study)
NCT07307664	Not specified	RECRUITING	Increasing Germline Genetic Testing for Patients With Cancer