ADAM12

protein-coding

ADAM metallopeptidase domain 12, the group of ADAM metallopeptidase domain containing

Gene summary

This gene encodes a member of a family of proteins that are 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. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

MANE transcript

NM_001288973.2

Inheritance

—

ClinVar variants

U:119B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr10:126,012,381-126,388,477

External References & Databases

Ensembl (ENSG00000148848)

Transcript & Mutation Effects

hg38 • Region Span ~376.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADAM12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001288973.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	2 clinvar	3 clinvar	8
missense			115 clinvar	8 clinvar	2 clinvar	125
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	119	10	5	134

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001288973.2	RefSeq	NP_001275902.1	23	MANE Select
ENST00000448723.2	Ensembl	ENSP00000391268.2	23	MANE Select
NM_001288974.2	RefSeq	NP_001275903.1	19	Standard
NM_001288975.2	RefSeq	NP_001275904.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
role of egf receptor transactivation by gpcrs in cardiac hypertrophy
Invadopodia formation
Extracellular matrix organization
Signaling by EGFR

Biological Process

proteolysis
cell adhesion
myoblast fusion
extracellular matrix organization
positive regulation of angiogenesis

Molecular Function

metalloendopeptidase activity
metallopeptidase activity
SH3 domain binding
metal ion binding

Cellular Component

extracellular region
nucleoplasm
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368679
Coding exons: 23
Length: 376075
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125748
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.27	438	519	0.843	0.0000297	5925
Missense (PolyPhen)		152	222.91	0.6819		2491
Synonymous	0.103	196	198	0.991	0.0000123	1774
Loss of Function	3.77	19	46.9	0.405	0.00000245	551

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in skeletal muscle regeneration, specifically at the onset of cell fusion. Also involved in macrophage-derived giant cells (MGC) and osteoclast formation from mononuclear precursors (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.232

Intolerance Scores

LoFtool: 0.320
RVIS EVS: 0.01
RVIS percentile EVS: 54.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.436

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium