TMEM95

Summary

TMEM95 (transmembrane protein 95, HGNC:27898) is a protein-coding gene on chromosome 17p13.1, encoding Sperm-egg fusion protein TMEM95 (Q3KNT9). Sperm protein required for fusion of sperm with the egg membrane during fertilization.

Involved in fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in cytoplasmic vesicle and sperm plasma membrane. Predicted to be active in acrosomal membrane.

Source: NCBI Gene 339168 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001320436

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27898
Approved symbol	TMEM95
Name	transmembrane protein 95
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC129793, UNQ9390
Ensembl gene	ENSG00000182896
Ensembl biotype	protein_coding
OMIM	617814
Entrez	339168

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000330767, ENST00000389982, ENST00000576060

RefSeq mRNA: 3 — MANE Select: NM_001320436 NM_001320435, NM_001320436, NM_198154

CCDS: CCDS32546, CCDS82051, CCDS82052

Canonical transcript exons

ENST00000576060 — 7 exons

Exon	Start	End
ENSE00001296441	7356029	7356049
ENSE00001302064	7355838	7355918
ENSE00001323546	7356392	7356479
ENSE00001326371	7355586	7355642
ENSE00001525536	7356196	7356276
ENSE00001747228	7356599	7357219
ENSE00003903313	7355156	7355373

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 76.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0137 / max 15.3369, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159160	0.0137	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	76.36	gold quality
testis	UBERON:0000473	75.20	gold quality
right testis	UBERON:0004534	75.09	gold quality
sural nerve	UBERON:0015488	48.30	silver quality
lower esophagus mucosa	UBERON:0035834	46.36	silver quality
granulocyte	CL:0000094	43.05	silver quality
bone marrow cell	CL:0002092	42.71	gold quality
tibial nerve	UBERON:0001323	41.55	gold quality
mucosa of stomach	UBERON:0001199	39.33	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	36.28	gold quality
lymph node	UBERON:0000029	36.02	silver quality
placenta	UBERON:0001987	35.66	silver quality
smooth muscle tissue	UBERON:0001135	35.63	silver quality
urinary bladder	UBERON:0001255	35.55	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	35.49	gold quality
calcaneal tendon	UBERON:0003701	35.46	gold quality
mucosa of transverse colon	UBERON:0004991	35.46	gold quality
bone marrow	UBERON:0002371	35.09	gold quality
skeletal muscle tissue	UBERON:0001134	34.88	gold quality
tonsil	UBERON:0002372	34.85	gold quality
right uterine tube	UBERON:0001302	33.52	gold quality
vermiform appendix	UBERON:0001154	33.44	silver quality
duodenum	UBERON:0002114	33.06	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	33.02	gold quality
lower esophagus	UBERON:0013473	32.39	silver quality
lower esophagus muscularis layer	UBERON:0035833	32.34	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting TMEM95, 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-6748-5P	100.00	65.81	1057
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-5001-5P	99.05	66.76	1972

Literature-anchored findings (GeneRIF, showing 1)

• Human sperm TMEM95 binds eggs and facilitates membrane fusion. (PMID:36161911)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem95	ENSMUSG00000094845
rattus_norvegicus	Tmem95	ENSRNOG00000043507

Protein

Protein identifiers

Sperm-egg fusion protein TMEM95 — Q3KNT9 (reviewed: Q3KNT9)

Alternative names: Transmembrane protein 95

All UniProt accessions (1): Q3KNT9

UniProt curated annotations — full annotation on UniProt →

Function. Sperm protein required for fusion of sperm with the egg membrane during fertilization.

Subunit / interactions. Does not interact with sperm-egg fusion proteins IZUMO1 or IZUMO1R/JUNO.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane.

Tissue specificity. Spermatozoa (at protein level).

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the TMEM95 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q3KNT9-1	1	yes
Q3KNT9-2	2
Q3KNT9-3	3

RefSeq proteins (3): NP_001307364, NP_001307365, NP_937797 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027984	TMEM95	Family

Pfam: PF15203

UniProt features (23 total): helix 6, disulfide bond 4, splice variant 2, mutagenesis site 2, turn 2, strand 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7UX0	X-RAY DIFFRACTION	1.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3KNT9-F1	82.02	0.33

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 (4): 17–118, 20–121, 105–128, 109–134

Mutagenesis-validated functional residues (2):

Position	Phenotype
70	significant loss of sperm-binding to hamster egg membrane.
73	significant loss of sperm-binding to hamster egg membrane.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): RNGTGGGC_UNKNOWN, GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, HP1SITEFACTOR_Q6, TGANTCA_AP1_C, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, CYTAGCAAY_UNKNOWN, IK2_01, GOBP_PLASMA_MEMBRANE_FUSION, GOBP_MEMBRANE_ORGANIZATION, GOBP_FERTILIZATION, GOCC_ACROSOMAL_MEMBRANE

GO Biological Process (2): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), single fertilization (GO:0007338)

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

GO Cellular Component (4): acrosomal membrane (GO:0002080), sperm plasma membrane (GO:0097524), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
single fertilization	1
cellular process involved in reproduction in multicellular organism	1
fertilization	1
binding	1
acrosomal vesicle	1
secretory granule membrane	1
plasma membrane	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

376 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM95	SPACA6	W5XKT8	909
TMEM95	IZUMO1	Q8IYV9	873
TMEM95	DCST1	Q5T197	729
TMEM95	CFAP119	A1A4V9	707
TMEM95	DCST2	Q5T1A1	688
TMEM95	ARMC3	Q5W041	665
TMEM95	SOFU1	Q96L11	631
TMEM95	KRTAP9-7	A8MTY7	578
TMEM95	CDRT15L2	A8MXV6	571
TMEM95	IZUMO1R	A6ND01	525
TMEM95	TBC1D28	Q2M2D7	479
TMEM95	KRTAP9-8	Q9BYQ0	476
TMEM95	OR1E2	P47887	475
TMEM95	SLC35G3	Q8N808	447
TMEM95	CCDC144A	A2RUR9	447
TMEM95	SLC35G6	P0C7Q6	447

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TMEM95	CIB1	psi-mi:“MI:0915”(physical association)	0.560
SCAND1	TMEM95	psi-mi:“MI:0915”(physical association)	0.560
BRK1	TMEM95	psi-mi:“MI:0915”(physical association)	0.560
TMEM95	EXTL3	psi-mi:“MI:0914”(association)	0.530
TMEM95	CLGN	psi-mi:“MI:0914”(association)	0.350
TMEM95	NEMP1	psi-mi:“MI:0914”(association)	0.350
TMEM95	CIB1	psi-mi:“MI:0915”(physical association)	0.000
SCAND1	TMEM95	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): TMEM95 (Two-hybrid), CIB1 (Two-hybrid), EXTL3 (Affinity Capture-MS), POMGNT1 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), DHODH (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), GPAA1 (Affinity Capture-MS), PIGS (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CLGN (Affinity Capture-MS), CANX (Affinity Capture-MS), METTL9 (Affinity Capture-MS), BSCL2 (Affinity Capture-MS), EMC7 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA7, A0A3Q1LRJ2, A2T6Z6, E9Q8Q8, O46673, O77049, O88823, P01588, P07865, P22301, P29676, P43480, P46651, P48411, P51496, P51497, P51746, P55029, P79338, Q0Z972, Q25BC1, Q28374, Q28C41, Q2PE73, Q3KNT9, Q4VK74, Q5Q0V6, Q5ZJY9, Q6A2H4, Q6AY06, Q6H8S9, Q6H8T0, Q6H8T1, Q6H8T2, Q6UXV1, Q865X4, Q8BGT0, Q8CGK6, Q8CJ70, Q8IU54

Diamond homologs: A0A3Q1LRJ2, P0DJF3, Q3KNT9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

767 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7355334:G:GT	donor_gain	0.9800
17:7355335:A:T	donor_gain	0.9800
17:7356476:TG:T	donor_gain	0.9800
17:7356477:GG:G	donor_gain	0.9800
17:7356480:G:GG	donor_gain	0.9800
17:7355915:G:T	donor_gain	0.9500
17:7355916:A:T	donor_gain	0.9300
17:7355870:T:G	acceptor_gain	0.9100
17:7356050:G:GG	donor_gain	0.9100
17:7356478:GA:G	donor_gain	0.9100
17:7355901:C:G	donor_gain	0.9000
17:7356475:GTGGA:G	donor_gain	0.8900
17:7355649:TC:T	donor_gain	0.8800
17:7356477:GGA:G	donor_gain	0.8800
17:7356478:GAG:G	donor_gain	0.8800
17:7355369:CTTAG:C	donor_loss	0.8600
17:7355370:TTAG:T	donor_loss	0.8600
17:7355371:TAG:T	donor_loss	0.8600
17:7355372:AGGTA:A	donor_loss	0.8600
17:7355373:GG:G	donor_loss	0.8600
17:7355374:G:C	donor_loss	0.8600
17:7355375:T:A	donor_loss	0.8600
17:7355836:A:AG	acceptor_gain	0.8600
17:7355837:G:GG	acceptor_gain	0.8600
17:7355869:ATATT:A	acceptor_gain	0.8600
17:7355871:ATT:A	acceptor_gain	0.8600
17:7355901:C:CG	donor_gain	0.8600
17:7355873:T:A	acceptor_gain	0.8500
17:7355635:GGTCA:G	donor_gain	0.8400
17:7356047:GCC:G	donor_gain	0.8400

AlphaMissense

1126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7355881:G:C	W90C	0.981
17:7355881:G:T	W90C	0.981
17:7356254:G:C	W129C	0.978
17:7356254:G:T	W129C	0.978
17:7355364:T:C	F54L	0.970
17:7355366:T:A	F54L	0.970
17:7355366:T:G	F54L	0.970
17:7355631:T:C	L72P	0.963
17:7356034:T:C	C105R	0.962
17:7356219:T:C	C118R	0.959
17:7355617:G:C	K67N	0.958
17:7355617:G:T	K67N	0.958
17:7355365:T:G	F54C	0.957
17:7355626:A:C	R70S	0.957
17:7355626:A:T	R70S	0.957
17:7356221:C:G	C118W	0.957
17:7355356:T:G	F51C	0.956
17:7356251:C:G	C128W	0.956
17:7356267:T:C	C134R	0.956
17:7356034:T:A	C105S	0.955
17:7356035:G:C	C105S	0.955
17:7356218:C:A	N117K	0.954
17:7356218:C:G	N117K	0.954
17:7355883:T:C	L91P	0.952
17:7356219:T:A	C118S	0.952
17:7356220:G:C	C118S	0.952
17:7356036:T:G	C105W	0.951
17:7356250:G:A	C128Y	0.949
17:7356228:T:A	C121S	0.948
17:7356229:G:C	C121S	0.948

dbSNP variants (sampled 300 via entrez): RS1000335578 (17:7354528 G>C,T), RS1000430496 (17:7354202 T>C), RS1000706354 (17:7354589 A>G), RS1000987455 (17:7353345 G>A), RS1001654698 (17:7356121 A>C), RS1002613243 (17:7357638 A>G), RS1004047200 (17:7357002 G>A), RS1004105750 (17:7354209 G>A,T), RS1004200593 (17:7353891 T>C,G), RS1006446345 (17:7355481 C>A,T), RS1007582976 (17:7356439 G>A,T), RS1007903956 (17:7356658 A>G), RS1009005267 (17:7357570 A>G), RS1010346025 (17:7355095 G>A,T), RS1010857626 (17:7357053 T>A,C)

Disease associations

OMIM: gene MIM:617814 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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