ADAM9

ADAM metallopeptidase domain 9, the group of ADAM metallopeptidase domain containing

Basic information

Region (hg38): 8:38996754-39105445

Previous symbols: [ "CORD9" ]

Links

ENSG00000168615 ∙ NCBI:8754 ∙ OMIM:602713 ∙ HGNC:216 ∙ Uniprot:Q13443 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod dystrophy 9 (Moderate), mode of inheritance: AR
• cone-rod dystrophy 9 (Strong), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• cone-rod dystrophy 9 (Definitive), mode of inheritance: AR
• ADAM9-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone-rod dystrophy 9	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	Ophthalmologic	11581183; 19409519; 25091951

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAM9 gene.

• not provided (9 variants)
• Cone-rod dystrophy 9 (3 variants)
• Cone-rod dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAM9 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			6	81	4	91
missense			185	4	1	190
nonsense	7					7
start loss						0
frameshift	3	2				5
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			9	30	3	42
non coding			24	77	20	121
Total	11	5	218	162	25

Highest pathogenic variant AF is 0.00000658

Variants in ADAM9

This is a list of pathogenic ClinVar variants found in the ADAM9 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-38997046-C-G		Cone-rod dystrophy 9	Uncertain significance (Jan 15, 2018)
8-38997068-G-A		Inborn genetic diseases	Uncertain significance (Aug 24, 2023)
8-38997071-C-G			Uncertain significance (Jun 20, 2022)
8-38997073-GGC-G		Cone-rod dystrophy	Pathogenic (Dec 20, 2022)
8-38997078-G-A			Likely benign (Aug 17, 2022)
8-38997085-C-T			Uncertain significance (Aug 30, 2023)
8-38997090-G-A			Likely benign (Dec 03, 2023)
8-38997091-G-T			Uncertain significance (Sep 13, 2022)
8-38997092-G-A		Inborn genetic diseases	Uncertain significance (May 13, 2024)
8-38997107-G-C			Uncertain significance (Sep 22, 2023)
8-38997108-G-T			Likely benign (Jul 12, 2022)
8-38997119-T-G			Uncertain significance (Aug 10, 2023)
8-38997124-G-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
8-38997134-G-A		Inborn genetic diseases	Uncertain significance (Jan 07, 2022)
8-38997139-G-C			Uncertain significance (Jun 14, 2022)
8-38997141-C-A		not specified • Cone-rod dystrophy 9	Benign (Jan 31, 2024)
8-38997144-C-T			Likely benign (Dec 11, 2023)
8-38997155-G-A			Uncertain significance (Mar 12, 2022)
8-38997159-A-G			Uncertain significance (Oct 03, 2022)
8-38997164-G-T			Uncertain significance (May 01, 2023)
8-38997170-C-G			Likely benign (Aug 08, 2022)
8-39007893-A-G			Likely benign (Dec 15, 2023)
8-39007903-C-T		Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
8-39007926-A-G			Uncertain significance (Apr 18, 2022)
8-39007968-G-A			Likely benign (Oct 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAM9	protein_coding	protein_coding	ENST00000487273	22	108276

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0294	0.971	125720	1	27	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.90	329	442	0.745	0.0000218	5365
Missense in Polyphen		91	190.87	0.47677		2299
Synonymous	-0.00570	155	155	1.00	0.00000802	1521
Loss of Function	4.81	13	49.5	0.262	0.00000262	602

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.000392	0.000359
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5. May mediate cell-cell, cell- matrix interactions and regulate the motility of cells via interactions with integrins. {ECO:0000250|UniProtKB:Q61072}.
• Disease: DISEASE: Cone-rod dystrophy 9 (CORD9) [MIM:612775]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:19409519}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Copper homeostasis;Collagen degradation;Extracellular matrix organization;TCR;EGFR1;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.218

Intolerance Scores

• loftool: 0.458
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.98

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.685
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adam9
• Phenotype: pigmentation phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal 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); vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: activation of MAPKK activity;membrane protein ectodomain proteolysis;cell adhesion;cell-matrix adhesion;transforming growth factor beta receptor signaling pathway;integrin-mediated signaling pathway;response to manganese ion;cell migration;keratinocyte differentiation;cell adhesion mediated by integrin;positive regulation of cell adhesion mediated by integrin;cell-cell adhesion mediated by integrin;positive regulation of macrophage fusion;response to tumor necrosis factor;response to laminar fluid shear stress;monocyte activation;response to hydrogen peroxide;positive regulation of protein secretion;positive regulation of membrane protein ectodomain proteolysis;PMA-inducible membrane protein ectodomain proteolysis;response to glucocorticoid;positive regulation of keratinocyte migration;response to calcium ion;cellular response to lipopolysaccharide;response to antineoplastic agent
• Cellular component: extracellular space;focal adhesion;cell surface;integral component of membrane;basolateral plasma membrane;intrinsic component of external side of plasma membrane;extracellular exosome
• Molecular function: metalloendopeptidase activity;protein kinase C binding;integrin binding;protein binding;collagen binding;metallopeptidase activity;SH3 domain binding;laminin binding;metal ion binding