ADAM28

protein-coding

ADAM metallopeptidase domain 28, 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 biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene is a lymphocyte-expressed ADAM protein. This gene is present in a gene cluster with other members of the ADAM family on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MANE transcript

NM_014265.6

Inheritance

—

ClinVar variants

U:123B:12

Top phenotype

Hereditary spastic paraplegia

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr8:24,294,069-24,359,014

External References & Databases

Ensembl (ENSG00000042980)

Transcript & Mutation Effects

hg38 • Region Span ~64.9 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 ADAM28 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 6

Hereditary spastic paraplegiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014265.6. 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			1 clinvar	3 clinvar		4
missense			117 clinvar	8 clinvar	1 clinvar	126
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	123	11	1	135

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014265.6	RefSeq	NP_055080.2	23	MANE Select
ENST00000265769.9	Ensembl	ENSP00000265769.4	23	MANE Select
NM_001304351.2	RefSeq	NP_001291280.1	22	Standard
NM_021777.5	RefSeq	NP_068547.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alpha4 beta1 integrin signaling events

Biological Process

proteolysis
spermatogenesis

Molecular Function

metalloendopeptidase activity
metallopeptidase activity
metal ion binding

Cellular Component

extracellular region
mitochondrion
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265769
Coding exons: 23
Length: 64979
Individuals with no LoFs: 125543
Homozygous LoFs: 1
Heterozygous LoFs: 204
Defined: 125748
p: 0.000815

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.915	467	415	1.13	0.0000201	5172
Missense (PolyPhen)		158	151.64	1.042		1972
Synonymous	-0.428	149	143	1.05	0.00000730	1347
Loss of Function	0.676	39	43.8	0.890	0.00000204	580

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0013	notable
Latino/Admixed American	0.00091	0.00090	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.00049	0.00049	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00054	0.00053	rare
South Asian	0.0026	0.0025	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the adhesive and proteolytic events that occur during lymphocyte emigration or may function in ectodomain shedding of lymphocyte surface target proteins, such as FASL and CD40L. May be involved in sperm maturation.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.994
RVIS EVS: 0.76
RVIS percentile EVS: 86.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.122

Gene Damage Prediction

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