ADAM7

Summary

ADAM7 (ADAM metallopeptidase domain 7, HGNC:214) is a protein-coding gene on chromosome 8p21.2, encoding Disintegrin and metalloproteinase domain-containing protein 7 (Q9H2U9). Required for normal male fertility via maintenance of epithelial cell morphology in the caput epididymis and subsequently correct epididymis lumen structure required for sperm development.

This gene encodes a member of the ADAMs family of zinc proteases. These transmembrane proteins play roles in multiple processes including cell signaling, adhesion and migration. The encoded protein lacks protease activity and may play roles in protein-protein interactions and cell adhesion processes including sperm-egg fusion. Mutations in this gene may be involved in the progression of melanoma.

Source: NCBI Gene 8756 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 139 total
• MANE Select transcript: NM_003817

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:214
Approved symbol	ADAM7
Name	ADAM metallopeptidase domain 7
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	GP-83, EAPI
Ensembl gene	ENSG00000069206
Ensembl biotype	protein_coding
OMIM	607310
Entrez	8756

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000175238, ENST00000380789, ENST00000441335, ENST00000520720

RefSeq mRNA: 1 — MANE Select: NM_003817 NM_003817

CCDS: CCDS6045

Canonical transcript exons

ENST00000175238 — 22 exons

Exon	Start	End
ENSE00000433454	24499236	24499316
ENSE00000684969	24468767	24468820
ENSE00000684971	24482142	24482311
ENSE00000684972	24485277	24485361
ENSE00000684973	24487187	24487317
ENSE00000684974	24489159	24489333
ENSE00000684975	24490799	24490888
ENSE00000684978	24491903	24492098
ENSE00000684980	24492495	24492597
ENSE00000684982	24493043	24493229
ENSE00000684986	24500178	24500256
ENSE00000818517	24500790	24500895
ENSE00000980187	24442473	24442576
ENSE00000980188	24447186	24447262
ENSE00001109024	24465699	24465775
ENSE00001109028	24463882	24463960
ENSE00001158594	24466799	24466988
ENSE00001684127	24507480	24507535
ENSE00001724953	24508546	24509565
ENSE00001821350	24441026	24441160
ENSE00002714248	24501477	24501576
ENSE00003677101	24476433	24476504

Expression profiles

Bgee: expression breadth broad, 21 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7892 / max 1224.0507, expressed in 7 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87965	0.6190	6
87964	0.0643	4
87963	0.0575	3
87967	0.0378	3
87966	0.0106	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.99	gold quality
cauda epididymis	UBERON:0004360	99.66	gold quality
epididymis	UBERON:0001301	94.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.67	gold quality
caput epididymis	UBERON:0004358	83.79	gold quality
seminal vesicle	UBERON:0000998	82.38	gold quality
left testis	UBERON:0004533	64.47	gold quality
right testis	UBERON:0004534	63.93	gold quality
testis	UBERON:0000473	63.64	gold quality
body of pancreas	UBERON:0001150	62.23	gold quality
buccal mucosa cell	CL:0002336	56.58	gold quality
pancreatic ductal cell	CL:0002079	54.16	silver quality
endothelial cell	CL:0000115	54.15	gold quality
cerebellar vermis	UBERON:0004720	52.33	gold quality
endometrium epithelium	UBERON:0004811	52.33	gold quality
male germ cell	CL:0000015	52.30	silver quality
epithelium of nasopharynx	UBERON:0001951	51.93	gold quality
sperm	CL:0000019	50.91	silver quality
pancreas	UBERON:0001264	50.70	gold quality
quadriceps femoris	UBERON:0001377	50.61	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
epithelial cell of pancreas	CL:0000083	50.19	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
deltoid	UBERON:0001476	50.07	gold quality
tibia	UBERON:0000979	49.80	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
vastus lateralis	UBERON:0001379	49.50	gold quality
thymus	UBERON:0002370	49.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.83
E-HCAD-38	no	1466.82
E-GEOD-99795	no	12.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting ADAM7, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-10394-5P	99.65	66.83	1852

Literature-anchored findings (GeneRIF, showing 2)

• mutated ADAM27 and ADAM7 genes could play a role in melanoma progression. (PMID:21618342)
• ADAM7 promotes the proliferation and invasion in trophoblast cells. (PMID:34116022)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	adam10b	ENSDARG00000015502
danio_rerio	adam10a	ENSDARG00000053468
danio_rerio	adam9b	ENSDARG00000057138
mus_musculus	Adam7	ENSMUSG00000022056
rattus_norvegicus	Adam7	ENSRNOG00000014054
drosophila_melanogaster	mmd	FBGN0259110
drosophila_melanogaster	kuz	FBGN0259984
caenorhabditis_elegans	sup-17	WBGENE00006324
caenorhabditis_elegans		WBGENE00006804

Paralogs (20): ADAM22 (ENSG00000008277), ADAM28 (ENSG00000042980), ADAM11 (ENSG00000073670), ADAM2 (ENSG00000104755), ADAM23 (ENSG00000114948), ADAM20 (ENSG00000134007), ADAMDEC1 (ENSG00000134028), ADAM30 (ENSG00000134249), ADAM19 (ENSG00000135074), ADAM10 (ENSG00000137845), ADAM21 (ENSG00000139985), ADAM15 (ENSG00000143537), ADAM12 (ENSG00000148848), ADAM33 (ENSG00000149451), ADAM8 (ENSG00000151651), ADAM17 (ENSG00000151694), ADAM29 (ENSG00000168594), ADAM9 (ENSG00000168615), ADAM18 (ENSG00000168619), ADAM32 (ENSG00000197140)

Protein

Protein identifiers

Disintegrin and metalloproteinase domain-containing protein 7 — Q9H2U9 (reviewed: Q9H2U9)

Alternative names: Sperm maturation-related glycoprotein GP-83

All UniProt accessions (4): Q9H2U9, A0A384MTL6, C9JK28, E5RK87

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal male fertility via maintenance of epithelial cell morphology in the caput epididymis and subsequently correct epididymis lumen structure required for sperm development. Plays a role in sperm motility, flagella morphology and tyrosine phosphorylation during sperm capacitance. Plays a role in normal expression levels of HSPA5, ITM2B and ADAM2 in sperm both prior to and post-capacitation. This is a non catalytic metalloprotease-like protein.

Subunit / interactions. Interacts with ITM2B in sperm; the interaction increases following capacitation. Interacts with HSPA5 and CANX.

Subcellular location. Membrane.

Disease relevance. Has been found to be frequently mutated in melanoma. ADAM7 mutations may play a role in melanoma progression and metastasis. Expressed in melanoma cells but not in healthy melanocytes.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H2U9-1	1	yes
Q9H2U9-2	2

RefSeq proteins (1): NP_003808* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001590	Peptidase_M12B	Domain
IPR001762	Disintegrin_dom	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR006586	ADAM_Cys-rich	Domain
IPR018358	Disintegrin_CS	Conserved_site
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR034027	Reprolysin_adamalysin	Domain
IPR036436	Disintegrin_dom_sf	Homologous_superfamily

Pfam: PF00200, PF01421, PF01562, PF08516

UniProt features (44 total): sequence variant 20, glycosylation site 6, disulfide bond 4, sequence conflict 4, splice variant 2, topological domain 2, domain 2, signal peptide 1, propeptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2U9-F1	75.03	0.32

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): 310–389, 350–373, 352–357, 460–480

Glycosylation sites (6): 174, 184, 584, 668, 84, 167

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOCC_CELL_SURFACE, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, chr8p21, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_CELL_MATURATION, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT

GO Biological Process (5): epithelial cell morphogenesis (GO:0003382), proteolysis (GO:0006508), positive regulation of flagellated sperm motility (GO:1902093), positive regulation of sperm capacitation (GO:1902492), epididymis development (GO:1905867)

GO Molecular Function (4): metalloendopeptidase activity (GO:0004222), endopeptidase activity (GO:0004175), metallopeptidase activity (GO:0008237), metal ion binding (GO:0046872)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of reproductive process	2
peptidase activity	2
cellular anatomical structure	2
cell morphogenesis	1
epithelial cell development	1
protein metabolic process	1
positive regulation of cilium movement	1
flagellated sperm motility	1
regulation of flagellated sperm motility	1
positive regulation of cilium-dependent cell motility	1
sperm capacitation	1
positive regulation of multicellular organismal process	1
regulation of sperm capacitation	1
positive regulation of cell maturation	1
tube development	1
endopeptidase activity	1
metallopeptidase activity	1
cation binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAM7	FN1	P02751	560
ADAM7	ZNF511	Q8NB15	497
ADAM7	DCXR	Q7Z4W1	487
ADAM7	TEDDM1	Q5T9Z0	465
ADAM7	STRBP	Q96SI9	391
ADAM7	H7BY64	H7BY64	353
ADAM7	EMILIN1	Q9Y6C2	336
ADAM7	FRMD8	Q9BZ67	327
ADAM7	CRISP1	P54107	324
ADAM7	FAM72B	Q86X60	323
ADAM7	ADAMTSL5	Q6ZMM2	317
ADAM7	CIMAP1C	Q8IXM7	317
ADAM7	TEKT3	Q9BXF9	317
ADAM7	LCN6	P62502	312
ADAM7	TEKTIP1	A6NCJ1	307

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ADAM7	ATP2B2	psi-mi:“MI:0914”(association)	0.350
ADAM7	RIOK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (35): ZNF146 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), RHOF (Affinity Capture-MS), SLC7A11 (Affinity Capture-MS), SARDH (Affinity Capture-MS), BTAF1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), PPOX (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CMTM8 (Affinity Capture-MS), DDX19B (Affinity Capture-MS), IRAK1 (Affinity Capture-MS), NUBPL (Affinity Capture-MS)

ESM2 similar proteins: A0A1E1WVX2, A0A6B7FMR5, A3R0T9, A4PBQ9, B8K1W0, C0L2T8, C9E1R7, C9E1R8, D3TTC1, D6PXE8, G5EDW5, J3S830, J3SBP9, J9Z332, O35227, O93523, P0C6B6, P0C6E4, P0C7B0, P0CB14, P0DM87, P20164, P30403, Q072L5, Q14FJ4, Q28475, Q2EI26, Q2QA02, Q2UXQ5, Q2UXR0, Q3HTN1, Q3HTN2, Q63180, Q6X1T6, Q7LZ61, Q7T046, Q8QG88, Q8R534, Q90220, Q90282

Diamond homologs: A0A0B4U9L8, A0A6B7FMR5, A2CJE2, A2CJE3, A2CJE4, A3R0T9, A4PBQ9, A8QL48, A8QL49, A8QL59, B8K1W0, C0LZJ5, C5H5D1, C5H5D2, C5H5D3, C5H5D4, C5H5D5, C5H5D6, C9E1R8, C9E1S0, D3TTC1, D3TTC2, D5LMJ3, D6PXE8, D8VNS0, F8RKV9, F8RKW0, F8RKW1, F8S108, G5EFD5, J3S829, J3S830, J3SDW6, J3SDW8, O35227, O35674, O42138, O43184, O77780, O88839

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2919 predictions. Top by Δscore:

Variant	Effect	Δscore
8:24465693:TTTTA:T	acceptor_loss	1.0000
8:24465694:TTTA:T	acceptor_loss	1.0000
8:24465696:TA:T	acceptor_loss	1.0000
8:24465697:A:AG	acceptor_gain	1.0000
8:24465698:G:A	acceptor_loss	1.0000
8:24465698:G:GG	acceptor_gain	1.0000
8:24465757:G:GG	donor_gain	1.0000
8:24465770:TCTA:T	donor_gain	1.0000
8:24465774:AG:A	donor_loss	1.0000
8:24465775:GGTAA:G	donor_loss	1.0000
8:24465777:T:A	donor_loss	1.0000
8:24466796:CA:C	acceptor_loss	1.0000
8:24466797:A:AC	acceptor_loss	1.0000
8:24466797:AGG:A	acceptor_gain	1.0000
8:24466798:GGG:G	acceptor_gain	1.0000
8:24466984:TAAAA:T	donor_gain	1.0000
8:24466985:AAAA:A	donor_gain	1.0000
8:24466986:AAA:A	donor_gain	1.0000
8:24466986:AAAGT:A	donor_loss	1.0000
8:24466987:AA:A	donor_gain	1.0000
8:24466987:AAGT:A	donor_loss	1.0000
8:24466988:AGT:A	donor_loss	1.0000
8:24466989:G:GG	donor_gain	1.0000
8:24489157:A:AG	acceptor_gain	1.0000
8:24489158:G:GG	acceptor_gain	1.0000
8:24490786:T:TA	acceptor_gain	1.0000
8:24492598:G:GG	donor_gain	1.0000
8:24499317:G:GG	donor_gain	1.0000
8:24499322:A:G	donor_gain	1.0000
8:24500257:G:GG	donor_gain	1.0000

AlphaMissense

5030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:24485350:A:C	S317R	0.995
8:24485352:T:A	S317R	0.995
8:24485352:T:G	S317R	0.995
8:24465750:A:C	S122R	0.993
8:24465752:T:A	S122R	0.993
8:24465752:T:G	S122R	0.993
8:24489175:T:C	F370L	0.991
8:24489176:T:G	F370C	0.991
8:24489177:C:A	F370L	0.991
8:24489177:C:G	F370L	0.991
8:24466800:G:A	G131R	0.990
8:24466800:G:C	G131R	0.990
8:24466801:G:A	G131E	0.990
8:24492077:T:A	C511S	0.990
8:24492078:G:C	C511S	0.990
8:24493053:T:A	C556S	0.990
8:24493054:G:C	C556S	0.990
8:24447250:T:C	L74P	0.989
8:24487295:T:A	C357S	0.989
8:24487295:T:C	C357R	0.989
8:24487296:G:C	C357S	0.989
8:24499239:T:A	C616S	0.989
8:24499240:G:C	C616S	0.989
8:24465711:T:G	Y109D	0.988
8:24465717:G:A	G111R	0.988
8:24465717:G:C	G111R	0.988
8:24476473:G:C	R225P	0.987
8:24487215:C:A	A330E	0.987
8:24489176:T:C	F370S	0.987
8:24489178:A:C	S371R	0.987

dbSNP variants (sampled 300 via entrez): RS1000035619 (8:24495598 G>T), RS1000062055 (8:24450883 C>A,G,T), RS1000069137 (8:24480359 T>C), RS1000142853 (8:24492294 G>A), RS1000197705 (8:24459997 A>G), RS1000222904 (8:24456528 C>A), RS1000265683 (8:24458314 T>C), RS1000274285 (8:24497867 T>C), RS1000302314 (8:24485747 A>G), RS1000332767 (8:24453359 C>A,T), RS1000362628 (8:24498242 T>C), RS1000412584 (8:24503668 T>C), RS1000443152 (8:24486219 A>C), RS1000526339 (8:24447791 C>T), RS1000552245 (8:24455681 C>T)

Disease associations

OMIM: gene MIM:607310 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001760_2	White matter integrity	3.000000e-06
GCST003113_2	Cingulate cortical amyloid beta load	2.000000e-07
GCST003478_5	Hair greying	4.000000e-06
GCST009817_3	Clozapine-induced myocarditis in schizophrenia	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004641	white matter integrity
EFO:0005194	amyloid-beta measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
perfluorooctanoic acid	decreases expression	1
phenethyl isothiocyanate	affects binding	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arbutin	increases expression	1
Benzo(a)pyrene	affects methylation	1
Metribolone	increases expression	1

Clinical trials (associated diseases)

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