ADAM18

protein-coding

ADAM metallopeptidase domain 18, the group of ADAM metallopeptidase domain containing

Gene summary

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 biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature sperm surface protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

MANE transcript

NM_014237.3

Inheritance

—

ClinVar variants

U:91B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.23

Max pathogenic AF

—

Genomic locus

chr8:39,584,489-39,730,065

External References & Databases

Ensembl (ENSG00000168619)

Transcript & Mutation Effects

hg38 • Region Span ~145.6 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 ADAM18 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 95

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014237.3. 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			2 clinvar	2 clinvar		4
missense			87 clinvar	8 clinvar		95
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	91	10	0	101

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014237.3	RefSeq	NP_055052.1	20	MANE Select
ENST00000265707.10	Ensembl	ENSP00000265707.5	20	MANE Select
NM_001190956.2	RefSeq	NP_001177885.1	6	Standard
NM_001320313.2	RefSeq	NP_001307242.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
multicellular organism development
spermatogenesis
cell differentiation

Molecular Function

metalloendopeptidase activity
metallopeptidase activity

Cellular Component

membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265707
Coding exons: 20
Length: 145576
Individuals with no LoFs: 125391
Homozygous LoFs: 2
Heterozygous LoFs: 355
Defined: 125748
p: 0.00142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.579	406	374	1.08	0.0000181	4868
Missense (PolyPhen)		137	129.52	1.0578		1730
Synonymous	-1.49	150	129	1.17	0.00000646	1289
Loss of Function	-1.32	47	38.2	1.23	0.00000162	560

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0024	0.0023	notable
Latino/Admixed American	0.0024	0.0021	notable
Ashkenazi Jewish	0.0025	0.0023	notable
East Asian	0.0067	0.0063	notable
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.00073	0.00071	rare
South Asian	0.00043	0.00036	rare
Other	0.0017	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0820

Intolerance Scores

LoFtool: 0.610
RVIS EVS: 0.59
RVIS percentile EVS: 82.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0695

Gene Damage Prediction

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