CPAMD8

C3 and PZP like alpha-2-macroglobulin domain containing 8, the group of C3 and PZP like, alpha-2-macroglobulin domain containing

Basic information

Region (hg38): 19:16892950-17026815

Links

ENSG00000160111 ∙ NCBI:27151 ∙ OMIM:608841 ∙ HGNC:23228 ∙ Uniprot:Q8IZJ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• anterior segment dysgenesis 8 (Strong), mode of inheritance: AR
• anterior segment dysgenesis 8 (Moderate), mode of inheritance: AR
• anterior segment dysgenesis 8 (Strong), mode of inheritance: AR
• anterior segment dysgenesis 8 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anterior segement dysgenesis 8	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	27839872

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPAMD8 gene.

• not provided (251 variants)
• Inborn genetic diseases (120 variants)
• Anterior segment dysgenesis 8 (8 variants)
• CPAMD8-related condition (2 variants)
• Glaucoma 3A (1 variants)
• Abnormal anterior eye segment morphology (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPAMD8 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				39	29	68
missense			128	17	36	181
nonsense	3					3
start loss						0
frameshift	3	2				5
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region				3	9	12
non coding		3	12	6	79	100
Total	7	7	140	62	144

Highest pathogenic variant AF is 0.000131

Variants in CPAMD8

This is a list of pathogenic ClinVar variants found in the CPAMD8 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-16892978-T-G			Benign (May 10, 2021)
19-16893128-T-C			Benign/Likely benign (Aug 11, 2023)
19-16893179-C-T		Inborn genetic diseases	Likely benign (Sep 15, 2021)
19-16893187-G-A		Inborn genetic diseases	Likely benign (Mar 14, 2023)
19-16893221-C-A			Uncertain significance (Aug 05, 2022)
19-16893223-C-T		Inborn genetic diseases	Uncertain significance (Oct 22, 2021)
19-16893230-T-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
19-16893238-T-C			Benign (Jan 29, 2024)
19-16893245-C-T			Uncertain significance (Nov 02, 2022)
19-16893305-C-T		See cases • Inborn genetic diseases	Uncertain significance (Sep 09, 2022)
19-16893308-T-C		Inborn genetic diseases	Uncertain significance (Aug 01, 2022)
19-16893323-G-A		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
19-16895976-G-A			Benign (May 10, 2021)
19-16896136-A-C			Benign (May 11, 2021)
19-16896219-C-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
19-16896253-C-T		CPAMD8-related disorder	Benign/Likely benign (Dec 05, 2023)
19-16896260-G-C		CPAMD8-related disorder	Benign (Mar 18, 2022)
19-16896267-G-A		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
19-16896296-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
19-16896339-G-A			Benign (Nov 13, 2023)
19-16896346-G-A			Likely benign (Aug 22, 2022)
19-16896552-C-T			Benign (Jan 11, 2024)
19-16896565-C-G			Benign (Mar 19, 2022)
19-16896567-G-T			Benign (Jan 19, 2024)
19-16896579-C-T		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPAMD8	protein_coding	protein_coding	ENST00000443236	42	133868

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.92e-23	1.00	124613	0	228	124841	0.000914

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.167	1094	1.11e+3	0.986	0.0000678	12339
Missense in Polyphen		351	380.27	0.92303		4496
Synonymous	0.213	471	477	0.988	0.0000322	3977
Loss of Function	4.27	53	98.8	0.536	0.00000537	1030

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00130	0.00129
Ashkenazi Jewish	0.000201	0.000199
East Asian	0.00106	0.00106
Finnish	0.000233	0.000232
European (Non-Finnish)	0.00127	0.00124
Middle Eastern	0.00106	0.00106
South Asian	0.000691	0.000686
Other	0.000829	0.000824

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Anterior segment dysgenesis 8 (ASGD8) [MIM:617319]: A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD8 patients predominantly manifest iris and lens abnormalities, in the absence of retinal abnormalities or extra-ocular features. ASGD8 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:27839872}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.912
• rvis_EVS: 2.44
• rvis_percentile_EVS: 98.55

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.436
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.696

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vip
• Phenotype: immune system phenotype; 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: eye development;negative regulation of endopeptidase activity
• Cellular component: extracellular space;plasma membrane
• Molecular function: serine-type endopeptidase inhibitor activity