ADAM11

Summary

ADAM11 (ADAM metallopeptidase domain 11, HGNC:189) is a protein-coding gene on chromosome 17q21.31, encoding Disintegrin and metalloproteinase domain-containing protein 11 (O75078). Probable ligand for integrin in the brain.

This gene encodes a member of the ADAM (a disintegrin and metalloprotease) protein 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This gene represents a candidate tumor suppressor gene for human breast cancer based on its location within a minimal region of chromosome 17q21 previously defined by tumor deletion mapping. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 4185 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 121 total — 2 pathogenic
• MANE Select transcript: NM_002390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:189
Approved symbol	ADAM11
Name	ADAM metallopeptidase domain 11
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000073670
Ensembl biotype	protein_coding
OMIM	155120
Entrez	4185

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000200557, ENST00000355638, ENST00000535346, ENST00000587773, ENST00000588363, ENST00000952530

RefSeq mRNA: 2 — MANE Select: NM_002390 NM_001318933, NM_002390

CCDS: CCDS11486, CCDS82139

Canonical transcript exons

ENST00000200557 — 27 exons

Exon	Start	End
ENSE00000731850	44772399	44772466
ENSE00001368023	44779739	44781846
ENSE00002726882	44758988	44759260
ENSE00003458980	44778152	44778242
ENSE00003468656	44777482	44777601
ENSE00003491245	44773014	44773085
ENSE00003496406	44771756	44771831
ENSE00003496945	44777952	44778066
ENSE00003502397	44777166	44777265
ENSE00003505862	44776899	44776962
ENSE00003515054	44769718	44769794
ENSE00003519968	44777695	44777863
ENSE00003529997	44772857	44772931
ENSE00003536594	44775584	44775676
ENSE00003536722	44775394	44775465
ENSE00003576374	44774492	44774582
ENSE00003576735	44759722	44759897
ENSE00003600724	44774295	44774379
ENSE00003603838	44772267	44772333
ENSE00003610237	44776745	44776795
ENSE00003618513	44774698	44774749
ENSE00003622449	44771584	44771669
ENSE00003628201	44779222	44779239
ENSE00003642100	44769982	44770048
ENSE00003668199	44776127	44776207
ENSE00003671010	44773261	44773427
ENSE00003682830	44775212	44775311

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 97.83.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5102 / max 108.6769, expressed in 346 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161190	1.1618	324
161191	0.3365	114
161192	0.0119	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.83	gold quality
cerebellar hemisphere	UBERON:0002245	97.41	gold quality
cerebellar cortex	UBERON:0002129	97.30	gold quality
cerebellum	UBERON:0002037	95.75	gold quality
right frontal lobe	UBERON:0002810	93.63	gold quality
prefrontal cortex	UBERON:0000451	90.54	gold quality
frontal cortex	UBERON:0001870	89.23	gold quality
neocortex	UBERON:0001950	88.61	gold quality
cingulate cortex	UBERON:0003027	88.54	gold quality
anterior cingulate cortex	UBERON:0009835	88.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.37	gold quality
apex of heart	UBERON:0002098	88.25	gold quality
superior frontal gyrus	UBERON:0002661	87.73	gold quality
cerebral cortex	UBERON:0000956	87.21	gold quality
postcentral gyrus	UBERON:0002581	87.08	gold quality
parietal lobe	UBERON:0001872	86.67	gold quality
primary visual cortex	UBERON:0002436	86.37	gold quality
entorhinal cortex	UBERON:0002728	85.77	gold quality
Ammon’s horn	UBERON:0001954	85.62	gold quality
cerebellar vermis	UBERON:0004720	85.30	gold quality
occipital lobe	UBERON:0002021	84.69	gold quality
middle temporal gyrus	UBERON:0002771	84.58	gold quality
telencephalon	UBERON:0001893	83.34	gold quality
right atrium auricular region	UBERON:0006631	83.03	gold quality
cortical plate	UBERON:0005343	82.61	gold quality
temporal lobe	UBERON:0001871	82.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.40	gold quality
brain	UBERON:0000955	82.31	gold quality
central nervous system	UBERON:0001017	81.94	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	16.99
E-ANND-3	no	1.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting ADAM11, 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-4262	100.00	73.26	3931
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4764-5P	98.88	65.53	894

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adam11	ENSDARG00000079204
mus_musculus	Adam11	ENSMUSG00000020926
rattus_norvegicus	Adam11	ENSRNOG00000002753

Paralogs (20): ADAM22 (ENSG00000008277), ADAM28 (ENSG00000042980), ADAM7 (ENSG00000069206), 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 11 — O75078 (reviewed: O75078)

Alternative names: Metalloproteinase-like, disintegrin-like, and cysteine-rich protein

All UniProt accessions (4): O75078, B4DKD2, H7BY08, K7EKA8

UniProt curated annotations — full annotation on UniProt →

Function. Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein. Required for localization of the potassium channel subunit proteins KCNA1/KV1.1 and KCNA2/KV1.2 at cerebellar cortex basket cell distal terminals, is thereby involved in ephaptic inhibitory synchronization of Purkinje cell firing and response to stress. Plays a role in spatial learning and motor coordination. Involved in the nociceptive pain response to chemical-derived stimulation.

Subunit / interactions. Interacts with LGI1 and LGI4. Interacts with KCNA1/KV1.1, KCNA2/KV1.2, DLG4/PSD-95 and ADAM22.

Subcellular location. Presynaptic cell membrane. Perikaryon. Cell projection. Axon.

Tissue specificity. Expressed predominantly in brain. Slightly detected or not at all in other tissues.

Post-translational modifications. The precursor is cleaved by a furin endopeptidase.

Domain organisation. A conserved motif [AVN[ED]CD] within the disintegrin-like domain could be involved in the binding to the integrin receptor.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
O75078-1	Long, MDC-769	yes
O75078-2	Short, MDC-524

RefSeq proteins (2): NP_001305862, NP_002381* (*=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, PF23106

UniProt features (30 total): disulfide bond 7, glycosylation site 4, splice variant 4, domain 3, region of interest 2, sequence conflict 2, topological domain 2, signal peptide 1, propeptide 1, compositionally biased region 1, chain 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75078-F1	80.04	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.

Disulfide bonds (7): 349–433, 392–417, 394–401, 503–523, 677–692, 686–698, 700–709

Glycosylation sites (4): 96, 163, 605, 673

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5682910	LGI-ADAM interactions
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 163 (showing top): MYOGENIN_Q6, GOBP_BEHAVIOR, GOMF_METALLOPEPTIDASE_ACTIVITY, GCANCTGNY_MYOD_Q6, SP3_Q3, MEF2_02, HNF1_Q6, LHX3_01, GGGTGGRR_PAX4_03, GGCNKCCATNK_UNKNOWN, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, CDP_01, NKX62_Q2, GOBP_BEHAVIORAL_RESPONSE_TO_PAIN, GOBP_RESPONSE_TO_PAIN

GO Biological Process (6): proteolysis (GO:0006508), integrin-mediated signaling pathway (GO:0007229), multicellular organismal response to stress (GO:0033555), establishment of protein localization (GO:0045184), behavioral response to acetic acid induced pain (GO:0061367), behavioral response to formalin induced pain (GO:0061368)

GO Molecular Function (3): metalloendopeptidase activity (GO:0004222), integrin binding (GO:0005178), metallopeptidase activity (GO:0008237)

GO Cellular Component (9): plasma membrane (GO:0005886), axon (GO:0030424), presynaptic membrane (GO:0042734), perikaryon (GO:0043204), endomembrane system (GO:0012505), membrane (GO:0016020), extracellular matrix (GO:0031012), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
behavioral response to chemical pain	2
protein metabolic process	1
cell surface receptor signaling pathway	1
response to stress	1
multicellular organismal process	1
establishment of localization	1
endopeptidase activity	1
metallopeptidase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
peptidase activity	1
membrane	1
cell periphery	1
neuron projection	1
synaptic membrane	1
presynapse	1
neuronal cell body	1
vacuole	1
plasma membrane	1
external encapsulating structure	1
cell junction	1

Protein interactions and networks

STRING

1160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAM11	LGI1	O95970	703
ADAM11	LGI2	Q8N0V4	563
ADAM11	NEGR1	Q7Z3B1	457
ADAM11	LGI3	Q8N145	454
ADAM11	DLG4	P78352	450
ADAM11	KANSL1L	A0AUZ9	427
ADAM11	ADAMTSL5	Q6ZMM2	422
ADAM11	DLG2	Q15700	419
ADAM11	ADAMTSL4	Q6UY14	417
ADAM11	DLG1	Q12959	408
ADAM11	MEP1A	Q16819	406
ADAM11	LGI4	Q8N135	401
ADAM11	ERV3-1	Q14264	390
ADAM11	ERVFRD-1	P60508	389
ADAM11	VSIG1	Q86XK7	366

IntAct

14 interactions, top by confidence:

A	B	Type	Score
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
CBLN4	ADAM11	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
IGFL3	CBX4	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
DEFB107A	ZZEF1	psi-mi:“MI:0914”(association)	0.350
DEFB109B	CHST10	psi-mi:“MI:0914”(association)	0.350
DEFB110	NME2P1	psi-mi:“MI:0914”(association)	0.350
ADAM11	ADAM23	psi-mi:“MI:0914”(association)	0.350
MSMB	ADAM11	psi-mi:“MI:0914”(association)	0.350
ADAM11	STC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): ADAM11 (Affinity Capture-MS), ADAM11 (Affinity Capture-MS), ADAM11 (Affinity Capture-MS), ADAM11 (Affinity Capture-RNA), STC2 (Two-hybrid), ADAM11 (Affinity Capture-MS), ADAM11 (Affinity Capture-MS), ADAM11 (Affinity Capture-MS), ARF5 (Affinity Capture-MS), ADAM11 (Affinity Capture-MS), RDH13 (Affinity Capture-MS), ADAM11 (Affinity Capture-MS), ADAM11 (Affinity Capture-MS), ADAM23 (Affinity Capture-MS), JAK1 (Affinity Capture-MS)

ESM2 similar proteins: A4FV98, A5D7B1, A5PK51, A6QLN9, A8MUP2, D3ZVU9, O15527, O35595, O75078, O95848, P57775, Q05B60, Q06643, Q14728, Q14CX5, Q1LZB9, Q27HK4, Q2T9T5, Q2TBS1, Q3UGX3, Q4R3I0, Q4V892, Q58CT4, Q5E9H2, Q5RCI5, Q5SUV1, Q5TM22, Q642A6, Q6IA17, Q6PCB0, Q6XQN6, Q862Z7, Q8N8L6, Q8R2R5, Q8R2Z5, Q8R366, Q8WUG5, Q95JH0, Q95JH2, Q969P0

Diamond homologs: A2CJE2, A2CJE3, A2CJE4, A8QL59, C0LZJ5, C5FUK3, D4B1G0, D4DCV9, E9NW26, F8VQ03, G5EFD5, J3S830, O13766, O35227, O42596, O73795, O75077, O75078, O77780, O93515, O93517, O93518, P0C6B6, P0C6E3, P0C6R9, P0C7B0, P0DJ87, P0DM87, P17497, P23323, P31989, P83912, Q05910, Q0NZX6, Q0NZX7, Q0NZX8, Q0NZX9, Q0NZY0, Q13443, Q13444

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	97
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
145615	GRCh38/hg38 17q21.31(chr17:43934167-44854025)x1	Pathogenic
59586	GRCh38/hg38 17q21.31(chr17:43570878-44762377)x1	Pathogenic

SpliceAI

3003 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44759256:GCCCG:G	donor_gain	1.0000
17:44759258:CCGG:C	donor_loss	1.0000
17:44759261:G:GG	donor_gain	1.0000
17:44759261:GTG:G	donor_loss	1.0000
17:44759262:T:A	donor_loss	1.0000
17:44769716:A:AG	acceptor_gain	1.0000
17:44769717:G:GG	acceptor_gain	1.0000
17:44769717:GCCT:G	acceptor_gain	1.0000
17:44769795:G:GG	donor_gain	1.0000
17:44771667:GCA:G	donor_gain	1.0000
17:44771670:G:GG	donor_gain	1.0000
17:44771754:A:AG	acceptor_gain	1.0000
17:44771754:AGT:A	acceptor_gain	1.0000
17:44771754:AGTGG:A	acceptor_gain	1.0000
17:44771755:G:GG	acceptor_gain	1.0000
17:44771755:GT:G	acceptor_gain	1.0000
17:44771755:GTG:G	acceptor_gain	1.0000
17:44771755:GTGGG:G	acceptor_gain	1.0000
17:44771828:TCAGG:T	donor_loss	1.0000
17:44771831:GGTA:G	donor_loss	1.0000
17:44771832:GT:G	donor_loss	1.0000
17:44771833:T:A	donor_loss	1.0000
17:44772261:TTGCA:T	acceptor_loss	1.0000
17:44772262:TGCAG:T	acceptor_loss	1.0000
17:44772263:GCA:G	acceptor_loss	1.0000
17:44772265:AG:A	acceptor_gain	1.0000
17:44772266:GG:G	acceptor_gain	1.0000
17:44772855:AGGTC:A	acceptor_loss	1.0000
17:44772928:GCTG:G	donor_gain	1.0000
17:44772932:G:GG	donor_gain	1.0000

AlphaMissense

5005 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44775445:T:A	C458S	1.000
17:44775446:G:C	C458S	1.000
17:44775644:T:A	C485S	1.000
17:44775645:G:C	C485S	1.000
17:44775646:C:G	C485W	1.000
17:44776187:T:A	C516S	1.000
17:44776188:G:C	C516S	1.000
17:44776189:C:G	C516W	1.000
17:44778188:C:A	A741D	1.000
17:44771605:T:G	Y135D	0.999
17:44772906:T:C	L243P	0.999
17:44773314:G:C	W293C	0.999
17:44773314:G:T	W293C	0.999
17:44774730:T:A	C401S	0.999
17:44774730:T:C	C401R	0.999
17:44774731:G:C	C401S	0.999
17:44775231:T:C	F414L	0.999
17:44775232:T:G	F414C	0.999
17:44775233:C:A	F414L	0.999
17:44775233:C:G	F414L	0.999
17:44775412:T:A	C447S	0.999
17:44775413:G:C	C447S	0.999
17:44775420:C:A	N449K	0.999
17:44775420:C:G	N449K	0.999
17:44775440:A:T	E456V	0.999
17:44775445:T:C	C458R	0.999
17:44775446:G:A	C458Y	0.999
17:44775446:G:T	C458F	0.999
17:44775447:C:G	C458W	0.999
17:44775449:A:T	D459V	0.999

dbSNP variants (sampled 300 via entrez): RS1000181008 (17:44761246 A>G), RS1000341692 (17:44759555 C>G,T), RS1000429598 (17:44773745 G>C), RS1000609448 (17:44780391 G>A), RS1000695265 (17:44770456 G>C), RS1000781501 (17:44764659 G>A), RS1000945417 (17:44757747 C>T), RS1001185714 (17:44779560 G>A,C), RS1001363806 (17:44760872 G>A), RS1001371761 (17:44773196 G>A,T), RS1001457883 (17:44767411 G>A), RS1001596303 (17:44773206 C>T), RS1001614393 (17:44761194 C>T), RS1001818269 (17:44767321 C>G,T), RS1001882159 (17:44779605 C>A)

Disease associations

OMIM: gene MIM:155120 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010796_729	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
bufotalin	increases expression	1
propionaldehyde	increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
pentanal	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Malathion	increases methylation	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Sodium Selenite	decreases expression	1
Copper Sulfate	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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