ADAM22

ADAM metallopeptidase domain 22, the group of ADAM metallopeptidase domain containing

Basic information

Region (hg38): 7:87934143-88202889

Links

ENSG00000008277 ∙ NCBI:53616 ∙ OMIM:603709 ∙ HGNC:201 ∙ Uniprot:Q9P0K1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 61 (Moderate), mode of inheritance: AR
• developmental and epileptic encephalopathy, 61 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 61	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	27066583

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAM22 gene.

• Developmental and epileptic encephalopathy, 61 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAM22 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				14	1	15
missense	1		38	7	7	53
nonsense						0
start loss						0
frameshift		2				2
inframe indel				1		1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	6	5	12
non coding					2	2
Total	1	3	38	22	10

Variants in ADAM22

This is a list of pathogenic ClinVar variants found in the ADAM22 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-87934479-T-G		ADAM22-related disorder	Benign (Dec 31, 2019)
7-87934489-C-T			Likely benign (Sep 01, 2023)
7-87934536-G-C		Inborn genetic diseases	Uncertain significance (May 11, 2022)
7-87934542-G-A		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
7-87934542-G-T		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
7-87934559-G-A		ADAM22-related disorder	Benign (Dec 31, 2019)
7-87935035-C-T			Likely benign (Jul 01, 2023)
7-87935042-G-C		Inborn genetic diseases	Uncertain significance (Oct 04, 2024)
7-87935046-C-T			Likely benign (Apr 01, 2023)
7-87935067-C-T		Inborn genetic diseases	Uncertain significance (Apr 24, 2024)
7-87935073-G-A		Developmental and epileptic encephalopathy, 61	Benign/Likely benign (Sep 07, 2021)
7-87935103-C-T		ADAM22-related disorder	Benign (Sep 04, 2024)
7-87935137-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
7-87935167-G-T		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
7-87935181-C-G			Likely benign (Nov 01, 2022)
7-87935182-C-G		Developmental and epileptic encephalopathy, 61	Benign (Jul 14, 2021)
7-88075657-C-T		ADAM22-related disorder	Benign (Nov 01, 2024)
7-88075661-T-C		Inborn genetic diseases	Uncertain significance (Feb 09, 2022)
7-88075669-G-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
7-88075684-G-A		ADAM22-related disorder	Benign (Apr 10, 2019)
7-88108211-A-G			Likely benign (Mar 06, 2018)
7-88108218-C-T		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
7-88108219-C-T			Uncertain significance (Jan 06, 2024)
7-88108247-C-T		ADAM22-related disorder	Likely benign (Aug 01, 2019)
7-88114591-T-C			Uncertain significance (Jan 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAM22	protein_coding	protein_coding	ENST00000265727	31	268747

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.251	0.749	125141	0	30	125171	0.000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.34	349	496	0.704	0.0000253	5934
Missense in Polyphen		86	192.12	0.44764		2292
Synonymous	0.275	175	180	0.974	0.00000978	1651
Loss of Function	5.53	14	60.4	0.232	0.00000315	749

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000646	0.0000639
Ashkenazi Jewish	0.00	0.00
East Asian	0.000168	0.000165
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000160	0.000159
Middle Eastern	0.000168	0.000165
South Asian	0.0000981	0.0000980
Other	0.000166	0.000164

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein (PubMed:19692335). Involved in regulation of cell adhesion and spreading and in inhibition of cell proliferation. Neuronal receptor for LGI1. {ECO:0000269|PubMed:12589811, ECO:0000269|PubMed:15882968, ECO:0000269|PubMed:16385342, ECO:0000269|PubMed:19692335}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 61 (EIEE61) [MIM:617933]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE61 is an autosomal recessive condition characterized by onset of seizures in infancy. {ECO:0000269|PubMed:27066583}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Developmental Biology;LGI-ADAM interactions (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.768
• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.93

Haploinsufficiency Scores

• pHI: 0.326
• hipred: Y
• hipred_score: 0.793
• ghis: 0.584

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.523

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adam22
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: proteolysis;cell adhesion;negative regulation of cell adhesion;central nervous system development;adult locomotory behavior;myelination in peripheral nervous system
• Cellular component: plasma membrane;integral component of membrane;axon;glutamatergic synapse;integral component of postsynaptic density membrane
• Molecular function: metalloendopeptidase activity;integrin binding;protein binding