CA4

carbonic anhydrase 4, the group of Carbonic anhydrases

Basic information

Region (hg38): 17:60149941-60170899

Previous symbols: [ "RP17" ]

Links

ENSG00000167434 ∙ NCBI:762 ∙ OMIM:114760 ∙ HGNC:1375 ∙ Uniprot:P22748 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 17 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 17	AD	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	7581389; 9385361; 15090652; 15563508; 17652713

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CA4 gene.

• not provided (247 variants)
• Retinitis pigmentosa (28 variants)
• Inborn genetic diseases (14 variants)
• not specified (5 variants)
• Retinitis pigmentosa 17 (3 variants)
• Retinitis Pigmentosa, Dominant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CA4 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			1	51	3	55
missense	1	1	109	5	2	118
nonsense	2		2			4
start loss			1			1
frameshift		1	1			2
inframe indel			3			3
splice donor/acceptor (+/-2bp)		6	1			7
splice region			4	14		18
non coding			3	27	5	35
Total	3	8	121	83	10

Highest pathogenic variant AF is 0.0000131

Variants in CA4

This is a list of pathogenic ClinVar variants found in the CA4 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-60149959-G-C		Retinitis Pigmentosa, Dominant	Likely benign (Jun 14, 2016)
17-60149988-C-G		Retinitis pigmentosa	Benign (Jan 12, 2018)
17-60150011-G-C		Retinitis pigmentosa	Benign (Jan 13, 2018)
17-60150033-AGATGCG-A			Uncertain significance (Nov 27, 2023)
17-60150037-G-A			Uncertain significance (Aug 20, 2021)
17-60150038-C-A			Likely benign (Dec 23, 2023)
17-60150040-G-A			Likely benign (Apr 11, 2023)
17-60150042-T-C		not specified	Uncertain significance (Oct 03, 2023)
17-60150045-T-C			Uncertain significance (Jul 17, 2023)
17-60150051-C-T			Uncertain significance (Aug 14, 2023)
17-60150061-C-G			Likely benign (Oct 23, 2023)
17-60150067-C-G			Likely benign (May 25, 2022)
17-60150068-G-A			Uncertain significance (Dec 03, 2021)
17-60150074-C-T		Retinitis pigmentosa 17 • Retinitis pigmentosa • CA4-related disorder	Conflicting classifications of pathogenicity (Feb 14, 2024)
17-60150089-G-A			Uncertain significance (Jan 17, 2022)
17-60150092-G-T			Pathogenic (Feb 08, 2022)
17-60150102-C-A			Likely benign (Jul 14, 2020)
17-60150102-C-G		Retinitis pigmentosa • CA4-related disorder	Conflicting classifications of pathogenicity (Jan 07, 2024)
17-60150109-C-G			Likely benign (Jul 29, 2022)
17-60150110-G-A			Likely benign (Aug 23, 2022)
17-60150110-G-C			Benign (Jan 25, 2024)
17-60155301-C-G			Likely benign (Oct 13, 2022)
17-60155301-C-T			Likely benign (Sep 27, 2023)
17-60155308-C-T			Likely benign (Jan 23, 2020)
17-60155314-A-C			Uncertain significance (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CA4	protein_coding	protein_coding	ENST00000300900	8	20964

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000713	0.741	125732	0	15	125747	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.122	179	174	1.03	0.0000101	2002
Missense in Polyphen		62	62.007	0.99989		748
Synonymous	-1.50	98	80.9	1.21	0.00000544	616
Loss of Function	1.15	10	14.8	0.678	6.51e-7	176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000125	0.000123
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000543	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000342	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid. {ECO:0000269|PubMed:15563508}.
• Pathway: Proximal tubule bicarbonate reclamation - Homo sapiens (human);Nitrogen metabolism - Homo sapiens (human);Metabolism;O2/CO2 exchange in erythrocytes;Transport of small molecules;Erythrocytes take up oxygen and release carbon dioxide;Erythrocytes take up carbon dioxide and release oxygen;Reversible hydration of carbon dioxide (Consensus)

Recessive Scores

• pRec: 0.216

Intolerance Scores

• loftool: 0.529
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.27

Haploinsufficiency Scores

• pHI: 0.0853
• hipred: N
• hipred_score: 0.210
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.656

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Car4
• 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; skeleton phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: bicarbonate transport
• Cellular component: rough endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;Golgi apparatus;trans-Golgi network;plasma membrane;cell surface;membrane;basolateral plasma membrane;apical plasma membrane;transport vesicle membrane;secretory granule membrane;anchored component of external side of plasma membrane;brush border membrane;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: carbonate dehydratase activity;protein binding;zinc ion binding