TMEM31

Summary

TMEM31 (transmembrane protein 31, HGNC:28601) is a protein-coding gene on chromosome Xq22.2, encoding Transmembrane protein 31 (Q5JXX7).

Predicted to be located in membrane.

Source: NCBI Gene 203562 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 38 total — 3 pathogenic
• MANE Select transcript: NM_182541

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28601
Approved symbol	TMEM31
Name	transmembrane protein 31
Location	Xq22.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC39655
Ensembl gene	ENSG00000179363
Ensembl biotype	protein_coding
OMIM	301102
Entrez	203562

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000319560, ENST00000875245, ENST00000932779

RefSeq mRNA: 1 — MANE Select: NM_182541 NM_182541

CCDS: CCDS35359

Canonical transcript exons

ENST00000319560 — 3 exons

Exon	Start	End
ENSE00001240288	103713594	103714032
ENSE00001240294	103712236	103712360
ENSE00001423965	103710909	103711076

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 98.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1148 / max 74.8801, expressed in 13 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197046	0.0946	9
197047	0.0203	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.53	gold quality
right testis	UBERON:0004534	96.46	gold quality
left testis	UBERON:0004533	96.45	gold quality
testis	UBERON:0000473	93.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.09	gold quality
adult organism	UBERON:0007023	89.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.85	gold quality
tibialis anterior	UBERON:0001385	65.86	silver quality
hypothalamus	UBERON:0001898	64.84	gold quality
kidney epithelium	UBERON:0004819	64.65	gold quality
spinal cord	UBERON:0002240	64.57	gold quality
tibial nerve	UBERON:0001323	63.82	gold quality
right ovary	UBERON:0002118	63.61	gold quality
left ovary	UBERON:0002119	63.61	gold quality
putamen	UBERON:0001874	61.92	gold quality
nucleus accumbens	UBERON:0001882	61.71	gold quality
left uterine tube	UBERON:0001303	61.41	gold quality
metanephros cortex	UBERON:0010533	60.98	gold quality
endocervix	UBERON:0000458	60.95	gold quality
ovary	UBERON:0000992	60.19	gold quality
right uterine tube	UBERON:0001302	60.10	gold quality
substantia nigra	UBERON:0002038	60.04	gold quality
caudate nucleus	UBERON:0001873	59.53	gold quality
body of uterus	UBERON:0009853	59.28	gold quality
mucosa of stomach	UBERON:0001199	58.76	gold quality
amygdala	UBERON:0001876	58.73	gold quality
anterior cingulate cortex	UBERON:0009835	58.45	gold quality
deltoid	UBERON:0001476	58.29	gold quality
right frontal lobe	UBERON:0002810	58.16	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

Transmembrane protein 31 — Q5JXX7 (reviewed: Q5JXX7)

All UniProt accessions (2): Q5JXX7, A0A140VK58

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_872347* (*=MANE)

Domains & families (InterPro)

UniProt features (9 total): compositionally biased region 4, transmembrane region 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JXX7-F1	67.98	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): CCANNAGRKGGC_UNKNOWN, HOXA4_Q2, chrXq22, ZNF618_TARGET_GENES, GSE10239_NAIVE_VS_KLRG1INT_EFF_CD8_TCELL_UP, GSE15767_MED_VS_SCS_MAC_LN_DN, WTTGKCTG_UNKNOWN, GSE31082_DP_VS_CD4_SP_THYMOCYTE_DN, GSE32423_CTRL_VS_IL4_MEMORY_CD8_TCELL_UP, GSE32423_IL7_VS_IL7_IL4_NAIVE_CD8_TCELL_UP, GSE7852_LN_VS_THYMUS_TCONV_UP, GSE411_UNSTIM_VS_400MIN_IL6_STIM_SOCS3_KO_MACROPHAGE_UP, GSE557_CIITA_KO_VS_I_AB_KO_DC_UP, GSE8921_UNSTIM_0H_VS_TLR1_2_STIM_MONOCYTE_6H_DN, GSE8921_UNSTIM_VS_TLR1_2_STIM_MONOCYTE_6H_UP

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

260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM31	DBNDD2	Q9BQY9	451
TMEM31	SPACA9	Q96E40	445
TMEM31	TSPYL1	Q9H0U9	377
TMEM31	FMR1NB	Q8N0W7	356
TMEM31	REXO1	Q8N1G1	355
TMEM31	SYS1	Q8N2H4	354
TMEM31	PHF7	Q9BWX1	349
TMEM31	ADAD1	Q96M93	331
TMEM31	PASD1	Q8IV76	323
TMEM31	Q3LFD5	Q3LFD5	322
TMEM31	SPATA6	Q9NWH7	319
TMEM31	C5orf58	C9J3I9	305
TMEM31	LRP11	Q86VZ4	300
TMEM31	GTSF1	Q8WW33	298
TMEM31	SLC25A23	Q9BV35	295

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TMEM31	UBQLN1	psi-mi:“MI:0915”(physical association)	0.740
UBQLN1	TMEM31	psi-mi:“MI:0915”(physical association)	0.740
SGTA	TMEM31	psi-mi:“MI:0915”(physical association)	0.560
TMEM31	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
TMEM31	SGTA	psi-mi:“MI:0915”(physical association)	0.560
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530

BioGRID (203): TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid), TMEM31 (Two-hybrid)

ESM2 similar proteins: A0A023PXG7, A0A1B0GU33, A0MD30, A0MD32, A3EX98, A3EXD4, A4GZ95, A6NGY3, B9VXI8, E9PJ23, E9PQR5, F5H982, F5HB41, F5HF35, F5HFZ4, F5HGC2, F5HHT4, F8W1W9, O75200, O92277, O94339, P03240, P09706, P0C6G1, P0C6G2, P0CV32, P14334, P16722, P16765, P16776, P16794, P28954, P34290, P38612, P41754, P47022, P60528, P84406, Q04567, Q08588

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	17
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1526836	GRCh37/hg19 Xq22.1-22.2(chrX:102582446-103203574)	Pathogenic
691852	GRCh37/hg19 Xq22.2(chrX:102967297-103038606)x0	Pathogenic
830310	NC_000023.10:g.102632399_103221016del	Pathogenic

SpliceAI

683 predictions. Top by Δscore:

Variant	Effect	Δscore
X:103712226:A:AG	acceptor_gain	1.0000
X:103712232:CCAG:C	acceptor_loss	1.0000
X:103712233:CAG:C	acceptor_loss	1.0000
X:103712234:A:AG	acceptor_gain	1.0000
X:103712234:AG:A	acceptor_gain	1.0000
X:103712234:AGGT:A	acceptor_gain	1.0000
X:103712235:G:GA	acceptor_gain	1.0000
X:103712235:GG:G	acceptor_gain	1.0000
X:103712235:GGT:G	acceptor_gain	1.0000
X:103712235:GGTG:G	acceptor_gain	1.0000
X:103713514:ACTC:A	donor_loss	1.0000
X:103713516:TCACC:T	donor_loss	1.0000
X:103713517:CACCA:C	donor_loss	1.0000
X:103712225:T:G	acceptor_gain	0.9900
X:103712227:T:G	acceptor_gain	0.9900
X:103712232:CCAGG:C	acceptor_gain	0.9900
X:103712234:AGGTG:A	acceptor_gain	0.9900
X:103712235:GGTGA:G	acceptor_gain	0.9900
X:103712243:CTTTA:C	acceptor_gain	0.9900
X:103712370:G:GA	donor_gain	0.9900
X:103713513:TAC:T	donor_loss	0.9900
X:103713518:A:AC	donor_gain	0.9900
X:103713519:C:CC	donor_gain	0.9900
X:103711031:TGA:T	donor_gain	0.9800
X:103711118:A:G	donor_gain	0.9800
X:103712231:CCCAG:C	acceptor_gain	0.9800
X:103712233:CAGGT:C	acceptor_gain	0.9800
X:103712356:AACAG:A	donor_loss	0.9800
X:103712358:CAGGC:C	donor_loss	0.9800
X:103712359:AGGCA:A	donor_loss	0.9800

AlphaMissense

1098 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:103713642:A:G	W321R	0.960
X:103713630:A:G	C325R	0.958
X:103713628:A:C	C325W	0.943
X:103713598:C:A	E335D	0.934
X:103713598:C:G	E335D	0.934
X:103713613:G:C	F330L	0.931
X:103713613:G:T	F330L	0.931
X:103713615:A:G	F330L	0.931
X:103713608:G:T	A332D	0.888
X:103713611:G:T	A331D	0.885
X:103713619:A:C	F328L	0.885
X:103713619:A:T	F328L	0.885
X:103713621:A:G	F328L	0.885
X:103713597:A:G	Y336H	0.837
X:103713780:T:C	F97L	0.835
X:103713782:T:A	F97L	0.835
X:103713782:T:G	F97L	0.835
X:103713594:C:G	A337P	0.832
X:103713600:C:T	E335K	0.830
X:103713654:C:G	A317P	0.827
X:103713640:C:A	W321C	0.826
X:103713640:C:G	W321C	0.826
X:103713792:T:C	F101L	0.810
X:103713794:T:A	F101L	0.810
X:103713794:T:G	F101L	0.810
X:103713612:C:G	A331P	0.807
X:103713636:C:G	A323P	0.796
X:103713646:G:C	D319E	0.794
X:103713646:G:T	D319E	0.794
X:103713653:G:T	A317E	0.785

dbSNP variants (sampled 300 via entrez): RS1000464531 (X:103711018 G>C), RS1000516223 (X:103710632 C>G), RS1000649627 (X:103712914 C>G,T), RS1001693127 (X:103714114 G>A), RS1001923670 (X:103711606 A>C), RS1002012177 (X:103711856 T>C), RS1002441411 (X:103711963 C>G,T), RS1002534833 (X:103712505 G>C,T), RS1003707537 (X:103710188 A>G), RS1005081110 (X:103709875 T>C), RS1005101706 (X:103713518 A>G), RS1005297095 (X:103714394 G>A), RS1005445916 (X:103711877 T>C), RS1006309467 (X:103711908 G>A), RS1007581497 (X:103713122 C>G)

Disease associations

OMIM: gene MIM:301102 | disease phenotypes: MIM:312920

GenCC curated gene-disease

Mondo (1): hereditary spastic paraplegia 2 (MONDO:0010733)

Orphanet (1): Spastic paraplegia type 2 (Orphanet:99015)

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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	6
Cadmium	decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tunicamycin	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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