ADAM30

Summary

ADAM30 (ADAM metallopeptidase domain 30, HGNC:208) is a protein-coding gene on chromosome 1p12, encoding Disintegrin and metalloproteinase domain-containing protein 30 (Q9UKF2). Plays a role in lysosomal amyloid precursor protein (APP) processing by cleaving and activating CTSD/cathepsin D which leads to APP degradation.

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This gene is testis-specific and contains a polymorphic region, resulting in isoforms with varying numbers of C-terminal repeats.

Source: NCBI Gene 11085 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 140 total — 4 pathogenic
• MANE Select transcript: NM_021794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:208
Approved symbol	ADAM30
Name	ADAM metallopeptidase domain 30
Location	1p12
Locus type	gene with protein product
Status	Approved
Aliases	svph4
Ensembl gene	ENSG00000134249
Ensembl biotype	protein_coding
OMIM	604779
Entrez	11085

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000369400

RefSeq mRNA: 1 — MANE Select: NM_021794 NM_021794

CCDS: CCDS907

Canonical transcript exons

ENST00000369400 — 1 exons

Exon	Start	End
ENSE00001449954	119893533	119896515

Expression profiles

Bgee: expression breadth broad, 15 present calls, max score 95.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0477 / max 37.4401, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14094	0.0311	4
14093	0.0166	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.53	gold quality
male germ cell	CL:0000015	93.17	gold quality
left testis	UBERON:0004533	81.80	gold quality
right testis	UBERON:0004534	80.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.57	gold quality
testis	UBERON:0000473	80.52	gold quality
buccal mucosa cell	CL:0002336	75.93	silver quality
adult organism	UBERON:0007023	73.18	gold quality
tongue squamous epithelium	UBERON:0006919	70.72	gold quality
type B pancreatic cell	CL:0000169	68.79	gold quality
triceps brachii	UBERON:0001509	67.86	gold quality
gluteal muscle	UBERON:0002000	67.25	gold quality
endothelial cell	CL:0000115	64.92	gold quality
olfactory bulb	UBERON:0002264	63.32	gold quality
pancreatic ductal cell	CL:0002079	59.12	silver quality
metanephric glomerulus	UBERON:0004736	56.49	gold quality
jejunal mucosa	UBERON:0000399	55.57	gold quality
quadriceps femoris	UBERON:0001377	55.51	gold quality
upper leg skin	UBERON:0004262	55.35	silver quality
vastus lateralis	UBERON:0001379	55.34	gold quality
deltoid	UBERON:0001476	55.32	gold quality
kidney epithelium	UBERON:0004819	54.79	gold quality
tibialis anterior	UBERON:0001385	54.73	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	54.69	gold quality
inferior olivary complex	UBERON:0002127	54.46	gold quality
renal glomerulus	UBERON:0000074	54.41	gold quality
nephron tubule	UBERON:0001231	54.36	gold quality
epithelial cell of pancreas	CL:0000083	54.15	gold quality
left ventricle myocardium	UBERON:0006566	53.19	gold quality
Brodmann (1909) area 46	UBERON:0006483	52.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting ADAM30, 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-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 1)

• Expression of a biologically inactive ADAM30 mutation did not affect amyloid beta proteins secretion. (PMID:27333034)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	adam10b	ENSDARG00000015502
danio_rerio	adam10a	ENSDARG00000053468
danio_rerio	adam9b	ENSDARG00000057138
mus_musculus	Adam30	ENSMUSG00000043468
rattus_norvegicus	Adam30	ENSRNOG00000019044
drosophila_melanogaster	mmd	FBGN0259110
drosophila_melanogaster	kuz	FBGN0259984
caenorhabditis_elegans	sup-17	WBGENE00006324
caenorhabditis_elegans		WBGENE00006804

Paralogs (20): ADAM22 (ENSG00000008277), ADAM28 (ENSG00000042980), ADAM7 (ENSG00000069206), ADAM11 (ENSG00000073670), ADAM2 (ENSG00000104755), ADAM23 (ENSG00000114948), ADAM20 (ENSG00000134007), ADAMDEC1 (ENSG00000134028), 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 30 — Q9UKF2 (reviewed: Q9UKF2)

All UniProt accessions (1): Q9UKF2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in lysosomal amyloid precursor protein (APP) processing by cleaving and activating CTSD/cathepsin D which leads to APP degradation.

Subunit / interactions. Interacts with CTSD; this leads to activation of CTSD.

Subcellular location. Late endosome membrane.

Tissue specificity. Expressed in brain neurons (at protein level). Expressed in testis.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKF2-1	Alpha	yes
Q9UKF2-2	Beta

RefSeq proteins (1): NP_068566* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
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 (43 total): disulfide bond 7, repeat 5, glycosylation site 5, binding site 4, mutagenesis site 3, domain 3, region of interest 2, compositionally biased region 2, topological domain 2, sequence variant 2, signal peptide 1, propeptide 1, short sequence motif 1, active site 1, chain 1, splice variant 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKF2-F1	79.68	0.51

Functional residue map

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

Catalytic / active sites (1): 339

Ligand- & substrate-binding residues (4): 172 (in inhibited form); 338; 342; 348

Disulfide bonds (7): 313–388, 353–373, 355–361, 457–477, 633–644, 638–650, 652–661

Glycosylation sites (5): 222, 372, 438, 473, 625

Mutagenesis-validated functional residues (3):

Position	Phenotype
338	loss of enzymatic activity; when associated with l-342 and l-348.
342	loss of enzymatic activity; when associated with l-338 and l-348.
348	loss of enzymatic activity; when associated with l-338 and l-342.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2534343	Interaction With Cumulus Cells And The Zona Pellucida
R-HSA-1187000	Fertilization
R-HSA-1474165	Reproduction

MSigDB gene sets: 75 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GOCC_CELL_SURFACE, MODULE_331, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_SEX_DIFFERENTIATION, chr1p12, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, GOBP_MALE_SEX_DIFFERENTIATION, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, GOCC_LATE_ENDOSOME_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOBP_PROTEOLYSIS, GOCC_PLASMA_MEMBRANE_REGION, WEBER_METHYLATED_HCP_IN_SPERM_DN

GO Biological Process (2): proteolysis (GO:0006508), male gonad development (GO:0008584)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), late endosome membrane (GO:0031902), sperm head plasma membrane (GO:1990913), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Fertilization	1
Reproduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
gonad development	1
development of primary male sexual characteristics	1
endopeptidase activity	1
metallopeptidase activity	1
peptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1
late endosome	1
endosome membrane	1
sperm head	1
sperm plasma membrane	1
plasma membrane region	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAM30	CDC123	O75794	571
ADAM30	CDKAL1	Q5VV42	543
ADAM30	ADAMTS9	Q9P2N4	512
ADAM30	JAZF1	Q86VZ6	507
ADAM30	NOTCH2	Q04721	492
ADAM30	TSPAN8	P19075	485
ADAM30	CTSD	P07339	471
ADAM30	DEFB126	Q9BYW3	462
ADAM30	MYOZ3	Q8TDC0	460
ADAM30	SLC30A8	Q8IWU4	447
ADAM30	HHEX	Q03014	445
ADAM30	CAMK1D	Q8IU85	445
ADAM30	DLEU7	Q6UYE1	442
ADAM30	ANKS1B	Q7Z6G8	429
ADAM30	PRSS50	Q9UI38	425
ADAM30	SPAM1	P38567	425

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ADAM30	CTSD	psi-mi:“MI:2364”(proximity)	0.510
ADAM30		psi-mi:“MI:0570”(protein cleavage)	0.440
ADAM30	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
ADAM30	MBTPS2	psi-mi:“MI:0914”(association)	0.350
MUSK	DNAJC13	psi-mi:“MI:0914”(association)	0.350
ADAM30	ADAM10	psi-mi:“MI:0914”(association)	0.350
ADAM30	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): ADAM30 (Affinity Capture-MS), SEC11C (Affinity Capture-MS), FOXF2 (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), CANX (Affinity Capture-MS), USP30 (Affinity Capture-MS), MTF2 (Affinity Capture-MS), SPCS2 (Affinity Capture-MS), ADAMTS2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), METTL7B (Affinity Capture-MS), LCLAT1 (Affinity Capture-MS), ADAM30 (Proximity Label-MS), ADAM30 (Proximity Label-MS), ADAMTS2 (Affinity Capture-MS)

ESM2 similar proteins: F8VQ03, O15072, O15204, O35227, O77780, P58397, P59509, P59510, P70505, P97776, P97857, Q1EHB3, Q28475, Q28478, Q28483, Q28660, Q3TTE0, Q5BK84, Q60411, Q60472, Q60718, Q60813, Q63180, Q63202, Q68SA9, Q811B3, Q811Q4, Q8C9W3, Q8K410, Q8N2E2, Q8R534, Q8TC27, Q8TE59, Q99965, Q9H2U9, Q9JI76, Q9JLN6, Q9R0X2, Q9R157, Q9R158

Diamond homologs: A0A0B4U9L8, A3R0T9, A4PBQ9, A8QL48, A8QL49, A8QL59, B8K1W0, C5H5D1, C5H5D2, C5H5D3, C5H5D4, C5H5D5, C5H5D6, C9E1R7, C9E1R8, C9E1S0, D3TTC1, D3TTC2, D5LMJ3, D8VNS0, F8S108, G5EDW5, J3S829, J3S830, J3SDW6, J3SDW8, J9Z332, O35674, O42138, O43184, O43506, O75077, O77780, O88839, O93523, P0C6B6, P0C6E8, P0C7B0, P0DM87, P0DM89

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	125
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1527270	GRCh37/hg19 1p13.3-11.2(chr1:111647582-121343783)	Pathogenic
154886	GRCh38/hg38 1p21.1-12(chr1:104325484-119977655)x3	Pathogenic
4083494	GRCh37/hg19 1p13.1-11.2(chr1:116675753-121116815)x1	Pathogenic
58088	GRCh38/hg38 1p13.1-12(chr1:116059621-120130051)x3	Pathogenic

SpliceAI

132 predictions. Top by Δscore:

Variant	Effect	Δscore
1:119894227:CCA:C	acceptor_gain	0.9200
1:119894228:CAC:C	acceptor_gain	0.9200
1:119894207:T:C	acceptor_gain	0.8800
1:119894230:C:CC	acceptor_gain	0.8800
1:119894212:G:T	acceptor_gain	0.8100
1:119896127:G:A	donor_gain	0.7600
1:119894229:A:AC	acceptor_gain	0.7300
1:119896353:AG:A	donor_gain	0.7300
1:119894211:C:CT	acceptor_gain	0.7100
1:119896192:G:C	donor_gain	0.7100
1:119895966:G:C	donor_gain	0.7000
1:119894204:CACT:C	acceptor_gain	0.6700
1:119894228:CA:C	acceptor_gain	0.6700
1:119896160:G:T	donor_gain	0.6500
1:119894202:ATCAC:A	acceptor_gain	0.6200
1:119894203:TCACT:T	acceptor_gain	0.6200
1:119895194:A:C	acceptor_gain	0.5900
1:119894238:ATT:A	acceptor_gain	0.5800
1:119896354:G:C	donor_gain	0.5700
1:119895960:A:AC	donor_gain	0.5400
1:119896374:C:A	donor_gain	0.5400
1:119896448:C:A	donor_gain	0.5300
1:119896135:A:C	donor_gain	0.5200
1:119894207:TTGCC:T	acceptor_gain	0.4900
1:119895961:T:C	donor_gain	0.4800
1:119894236:GGATT:G	acceptor_gain	0.4600
1:119894621:C:CA	acceptor_gain	0.4600
1:119896123:T:TA	donor_gain	0.4600
1:119894204:CACTT:C	acceptor_gain	0.4500
1:119894237:GATTA:G	acceptor_gain	0.4400

AlphaMissense

5221 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:119894580:C:G	C586S	0.998
1:119894581:A:T	C586S	0.998
1:119894661:C:G	C559S	0.998
1:119894662:A:T	C559S	0.998
1:119894817:C:G	C507S	0.998
1:119894818:A:T	C507S	0.998
1:119895215:A:C	S374R	0.998
1:119895215:A:T	S374R	0.998
1:119895217:T:G	S374R	0.998
1:119894772:C:G	C522S	0.997
1:119894773:A:T	C522S	0.997
1:119894946:C:G	C464S	0.997
1:119894947:A:T	C464S	0.997
1:119894576:C:A	W587C	0.996
1:119894576:C:G	W587C	0.996
1:119894579:G:C	C586W	0.996
1:119894660:A:C	C559W	0.996
1:119894662:A:G	C559R	0.996
1:119895225:C:A	S371I	0.996
1:119895571:A:G	W256R	0.996
1:119895571:A:T	W256R	0.996
1:119894581:A:G	C586R	0.995
1:119894676:C:G	C554S	0.995
1:119894677:A:T	C554S	0.995
1:119894773:A:G	C522R	0.995
1:119894805:A:C	F511C	0.995
1:119894816:G:C	C507W	0.995
1:119895228:A:C	F370C	0.995
1:119895255:C:G	C361S	0.995
1:119895256:A:T	C361S	0.995

dbSNP variants (sampled 300 via entrez): RS1001080821 (1:119897515 C>G), RS1001929737 (1:119894195 G>A,C), RS1004323205 (1:119893466 T>C), RS1004906912 (1:119895450 T>C), RS1005591450 (1:119895070 T>C), RS1005659107 (1:119893754 C>T), RS1006323299 (1:119896450 C>T), RS1006704655 (1:119893448 A>G), RS1008375396 (1:119896738 C>G,T), RS1008450363 (1:119897145 T>C), RS1008557678 (1:119896947 G>A,C), RS1009006564 (1:119896569 A>G), RS1009599314 (1:119897300 T>A), RS1010476640 (1:119893168 C>T), RS1011794436 (1:119897831 G>A)

Disease associations

OMIM: gene MIM:604779 | disease phenotypes: MIM:102500

GenCC curated gene-disease

Mondo (1): acroosteolysis dominant type (MONDO:0007057)

Orphanet (1): Hajdu-Cheney syndrome (Orphanet:955)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000167_8	Type 2 diabetes	4.000000e-08
GCST001729_14	Crohn’s disease	2.000000e-11
GCST005166_9	GIP levels in response to oral glucose tolerance test (120 minutes)	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004307	glucose tolerance test
EFO:0008464	glucose-dependent insulinotropic peptide measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535663	Acroosteolysis dominant type (supp.)
C537586	Serpentine fibula polycystic kidney syndrome (supp.)

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

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

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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