TMEM81

Summary

TMEM81 (transmembrane protein 81, HGNC:32349) is a protein-coding gene on chromosome 1q32.1, encoding Transmembrane protein 81 (Q6P7N7). Essential fertilization factor required for male fertility.

Enables protein-macromolecule adaptor activity. Involved in sperm-egg recognition. Is active in plasma membrane.

Source: NCBI Gene 388730 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_203376

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32349
Approved symbol	TMEM81
Name	transmembrane protein 81
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	UNQ2788, MGC75217, HC3107, KVLA2788
Ensembl gene	ENSG00000174529
Ensembl biotype	protein_coding
Entrez	388730

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000367167

RefSeq mRNA: 1 — MANE Select: NM_203376 NM_203376

CCDS: CCDS1450

Canonical transcript exons

ENST00000367167 — 1 exons

Exon	Start	End
ENSE00001443672	205083129	205084460

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 93.57.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	93.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.89	gold quality
cerebellar hemisphere	UBERON:0002245	82.82	gold quality
cerebellum	UBERON:0002037	82.77	gold quality
cerebellar cortex	UBERON:0002129	82.77	gold quality
cerebellar vermis	UBERON:0004720	82.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.98	gold quality
lower esophagus mucosa	UBERON:0035834	80.90	gold quality
quadriceps femoris	UBERON:0001377	79.62	gold quality
cortical plate	UBERON:0005343	79.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.80	gold quality
primary visual cortex	UBERON:0002436	77.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.63	gold quality
right frontal lobe	UBERON:0002810	77.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.39	gold quality
granulocyte	CL:0000094	77.36	gold quality
gastrocnemius	UBERON:0001388	77.09	gold quality
frontal cortex	UBERON:0001870	76.58	gold quality
ganglionic eminence	UBERON:0004023	76.50	gold quality
superior frontal gyrus	UBERON:0002661	76.38	gold quality
apex of heart	UBERON:0002098	76.37	gold quality
cerebral cortex	UBERON:0000956	76.14	gold quality
prefrontal cortex	UBERON:0000451	76.05	gold quality
muscle of leg	UBERON:0001383	75.49	gold quality
brain	UBERON:0000955	75.31	gold quality
right lobe of liver	UBERON:0001114	75.07	gold quality
anterior cingulate cortex	UBERON:0009835	75.06	gold quality
mucosa of transverse colon	UBERON:0004991	74.64	gold quality
putamen	UBERON:0001874	74.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	332.06
E-MTAB-6058	no	98.14
E-ANND-3	no	1.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting TMEM81, 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-6755-5P	99.95	65.59	464
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4298	97.26	66.59	765
HSA-MIR-197-5P	97.23	68.10	596
HSA-MIR-4327	97.21	67.71	676
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-2276-5P	96.27	65.85	937

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem81	ENSDARG00000042536
mus_musculus	Tmem81	ENSMUSG00000048174
rattus_norvegicus	Tmem81	ENSRNOG00000028752

Protein

Protein identifiers

Transmembrane protein 81 — Q6P7N7 (reviewed: Q6P7N7)

All UniProt accessions (1): Q6P7N7

UniProt curated annotations — full annotation on UniProt →

Function. Essential fertilization factor required for male fertility. Part of a conserved trimeric sperm complex with the essential fertilization factors IZUMO1 and SPACA6 which bridges sperm and oocyte membranes during fertilization by binding to IZUMO1R/JUNO on the oocyte.

Subunit / interactions. Forms a complex with IZUMO1 and SPACA6 on spermatocyte cell membrane required for fertilization.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in sperm (at protein level).

RefSeq proteins (1): NP_976310* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007110	Ig-like_dom	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR039293	TMEM81	Family

UniProt features (10 total): topological domain 2, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P7N7-F1	84.71	0.54

Functional residue map

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

Disulfide bonds (1): 104–160

Glycosylation sites (1): 45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_SINGLE_FERTILIZATION, AGGAAGC_MIR5163P, GOBP_SPERM_EGG_RECOGNITION, GOBP_FERTILIZATION, GOBP_CELL_CELL_RECOGNITION, HOXA4_Q2, TGGAAA_NFAT_Q4_01, HMGIY_Q6, KOYAMA_SEMA3B_TARGETS_DN, MARTENS_TRETINOIN_RESPONSE_UP, STAT6_01, GSE10094_LCMV_VS_LISTERIA_IND_EFF_CD4_TCELL_UP, MIR642A_5P, MIR3132, MIR197_5P

GO Biological Process (1): sperm-egg recognition (GO:0035036)

GO Molecular Function (1): protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
single fertilization	1
cell-cell recognition	1
protein binding	1
molecular adaptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM81	DSTYK	Q6XUX3	506
TMEM81	TMEM120B	A0PK00	433
TMEM81	CORO7	P57737	431
TMEM81	CNTN2	P78432	431
TMEM81	RBBP5	Q15291	398
TMEM81	TMCC2	O75069	398
TMEM81	GOLT1A	Q6ZVE7	397
TMEM81	BET1L	Q9NYM9	397
TMEM81	NAGA	P17050	388
TMEM81	LRRN2	O75325	374
TMEM81	BDH2	Q9BUT1	369
TMEM81	SEC61G	P38384	368
TMEM81	ZC3H11A	O75152	366
TMEM81	REEP3	Q6NUK4	366
TMEM81	RERE	Q9P2R6	364

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CNTN5	TMEM81	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (4): TMEM81 (Affinity Capture-RNA), TMEM81 (Affinity Capture-Western), TMEM81 (Affinity Capture-Western), SPACA6P (Affinity Capture-Western)

ESM2 similar proteins: A0A2R8QHQ6, A0A8M9PDM1, A6PWV3, A6QL94, D3Z690, F5HC71, O02699, O12980, O77515, P04401, P05402, P0DJF3, P0DP43, P12401, P17150, P18917, P19159, P20826, P21583, P21702, P33579, P33580, P46685, P52173, P79169, Q08125, Q14512, Q28586, Q29030, Q4R6V5, Q5VZ72, Q60440, Q62575, Q6AY06, Q6P7N7, Q920I0, Q95J76, Q95MD2, Q95N18, Q9CQ58

Diamond homologs: B8JI67, Q0VCB1, Q6AXW8, Q6P7N7, Q9D5K1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

367 predictions. Top by Δscore:

Variant	Effect	Δscore
1:205083340:A:T	acceptor_gain	0.6900
1:205083503:T:TA	donor_gain	0.6700
1:205083745:C:CC	acceptor_gain	0.6600
1:205083723:A:C	donor_gain	0.6500
1:205083351:C:CT	acceptor_gain	0.6300
1:205083422:T:C	donor_gain	0.6100
1:205083688:G:C	donor_gain	0.6100
1:205083375:A:AC	donor_gain	0.6000
1:205083376:C:CC	donor_gain	0.6000
1:205083385:G:C	donor_gain	0.5800
1:205083482:C:A	donor_gain	0.5800
1:205083351:C:T	acceptor_gain	0.5700
1:205083376:CTGCG:C	donor_gain	0.5700
1:205083592:CCTCA:C	donor_loss	0.5700
1:205083594:T:TA	donor_loss	0.5700
1:205083595:CA:C	donor_loss	0.5700
1:205083597:CC:C	donor_loss	0.5700
1:205083635:C:A	donor_gain	0.5700
1:205083384:AGCT:A	donor_gain	0.5600
1:205083414:C:CA	donor_gain	0.5600
1:205083444:C:A	donor_gain	0.5600
1:205083744:A:AC	acceptor_gain	0.5600
1:205083788:AAC:A	donor_gain	0.5600
1:205083339:C:CT	acceptor_gain	0.5500
1:205083421:ATT:A	donor_gain	0.5500
1:205083628:T:TA	donor_gain	0.5500
1:205083716:T:C	donor_gain	0.5500
1:205083452:G:C	donor_gain	0.5400
1:205083481:C:CA	donor_gain	0.5300
1:205083612:CCA:C	donor_gain	0.5200

AlphaMissense

1650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:205083845:C:G	R159P	0.997
1:205083958:C:A	W121C	0.997
1:205083958:C:G	W121C	0.997
1:205083842:C:G	C160S	0.996
1:205083843:A:T	C160S	0.996
1:205083960:A:G	W121R	0.996
1:205083960:A:T	W121R	0.996
1:205083843:A:G	C160R	0.993
1:205083849:A:C	Y158D	0.993
1:205083842:C:T	C160Y	0.992
1:205083841:A:C	C160W	0.991
1:205083855:C:A	G156W	0.991
1:205083917:A:C	F135C	0.991
1:205083854:C:T	G156E	0.990
1:205084011:A:G	C104R	0.990
1:205084079:C:G	C81S	0.990
1:205084080:A:G	C81R	0.990
1:205084080:A:T	C81S	0.990
1:205084009:A:C	C104W	0.989
1:205084133:C:G	C63S	0.989
1:205084134:A:G	C63R	0.989
1:205084134:A:T	C63S	0.989
1:205084176:A:G	C49R	0.989
1:205083842:C:A	C160F	0.988
1:205084010:C:T	C104Y	0.988
1:205084061:C:G	C87S	0.988
1:205084062:A:T	C87S	0.988
1:205084163:C:G	C53S	0.988
1:205084164:A:T	C53S	0.988
1:205084174:A:C	C49W	0.988

dbSNP variants (sampled 300 via entrez): RS1001301775 (1:205085771 T>C), RS1001691998 (1:205086051 A>G), RS1002992800 (1:205082739 G>T), RS1003243198 (1:205083013 AGACAATT>A), RS1006434463 (1:205085369 A>C), RS1007051528 (1:205084968 G>C), RS1007408816 (1:205085408 A>G), RS1008224368 (1:205083559 C>G), RS1009985345 (1:205085508 G>A), RS1010678148 (1:205083921 C>G,T), RS1013194145 (1:205085534 A>G), RS1015678746 (1:205084321 G>T), RS1016423765 (1:205085854 G>T), RS1017330278 (1:205086198 C>T), RS1017931776 (1:205086204 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST007324_22	Adventurousness	5.000000e-10
GCST010697_12	Cortical surface area (min-P)	6.000000e-10
GCST010698_16	Subcortical volume (min-P)	8.000000e-09
GCST010699_52	Brain morphology (min-P)	5.000000e-08
GCST010700_66	Cortical thickness (MOSTest)	3.000000e-09
GCST010701_17	Cortical surface area (MOSTest)	5.000000e-08
GCST010702_2	Subcortical volume (MOSTest)	3.000000e-08
GCST010703_27	Brain morphology (MOSTest)	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
trichostatin A	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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