CA8

Summary

CA8 (carbonic anhydrase 8 (inactive), HGNC:1382) is a protein-coding gene on chromosome 8q12.1, encoding Carbonic anhydrase-related protein (P35219). Does not have a carbonic anhydrase catalytic activity.

The protein encoded by this gene was initially named CA-related protein because of sequence similarity to other known carbonic anhydrase genes. However, the gene product lacks carbonic anhydrase activity (i.e., the reversible hydration of carbon dioxide). The gene product continues to carry a carbonic anhydrase designation based on clear sequence identity to other members of the carbonic anhydrase gene family. The absence of CA8 gene transcription in the cerebellum of the lurcher mutant in mice with a neurologic defect suggests an important role for this acatalytic form. Mutations in this gene are associated with cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CMARQ3). Polymorphisms in this gene are associated with osteoporosis, and overexpression of this gene in osteosarcoma cells suggests an oncogenic role. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 767 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 102 total — 6 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 21
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004056

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1382
Approved symbol	CA8
Name	carbonic anhydrase 8 (inactive)
Location	8q12.1
Locus type	gene with protein product
Status	Approved
Aliases	CARP, CA-RP, CA-VIII
Ensembl gene	ENSG00000178538
Ensembl biotype	protein_coding
OMIM	114815
Entrez	767

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000317995, ENST00000524872, ENST00000528666, ENST00000529918, ENST00000869784, ENST00000869785, ENST00000939218, ENST00000939219, ENST00000943617, ENST00000943618, ENST00000943619

RefSeq mRNA: 4 — MANE Select: NM_004056 NM_001321837, NM_001321838, NM_001321839, NM_004056

CCDS: CCDS6174

Canonical transcript exons

ENST00000317995 — 9 exons

Exon	Start	End
ENSE00001218692	60208750	60208919
ENSE00001360921	60185412	60189985
ENSE00002154258	60281048	60281400
ENSE00003479603	60279689	60279880
ENSE00003511738	60226873	60226935
ENSE00003524743	60222649	60222761
ENSE00003527892	60224537	60224585
ENSE00003626637	60265925	60266049
ENSE00003667870	60232284	60232379

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 89.38.

FANTOM5 (CAGE): breadth broad, TPM avg 7.5358 / max 249.7828, expressed in 683 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93254	7.5358	683

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	89.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.30	gold quality
cerebellar vermis	UBERON:0004720	83.26	gold quality
right testis	UBERON:0004534	82.18	gold quality
left testis	UBERON:0004533	81.41	gold quality
cerebellar cortex	UBERON:0002129	80.64	gold quality
cerebellar hemisphere	UBERON:0002245	80.46	gold quality
adenohypophysis	UBERON:0002196	80.24	gold quality
cerebellum	UBERON:0002037	80.15	gold quality
pituitary gland	UBERON:0000007	79.84	gold quality
caudate nucleus	UBERON:0001873	79.33	gold quality
testis	UBERON:0000473	78.88	gold quality
islet of Langerhans	UBERON:0000006	78.05	gold quality
amygdala	UBERON:0001876	77.52	gold quality
nucleus accumbens	UBERON:0001882	76.28	gold quality
anterior cingulate cortex	UBERON:0009835	76.12	gold quality
cingulate cortex	UBERON:0003027	76.04	gold quality
right atrium auricular region	UBERON:0006631	75.71	gold quality
calcaneal tendon	UBERON:0003701	75.29	gold quality
palpebral conjunctiva	UBERON:0001812	75.15	gold quality
apex of heart	UBERON:0002098	74.95	gold quality
body of stomach	UBERON:0001161	74.41	gold quality
heart left ventricle	UBERON:0002084	74.22	gold quality
prefrontal cortex	UBERON:0000451	74.17	gold quality
cardiac ventricle	UBERON:0002082	73.78	gold quality
rectum	UBERON:0001052	73.59	gold quality
putamen	UBERON:0001874	73.54	gold quality
stomach	UBERON:0000945	73.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	39.86
E-ANND-3	yes	5.38
E-CURD-112	no	305.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

93 targeting CA8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4517	99.76	69.19	1867

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 19)

• Overexpression of Carbonic anhydrase-related protein VIII promotes colon cancer cell growth (PMID:17219437)
• The results suggest that the variations of CA8 and CA10 loci may be important determinants of osteoporosis in Japanese women. (PMID:19172221)
• Crystal structure of human carbonic anhydrase-related protein VIII reveals the basis for catalytic silencing (PMID:19360879)
• Consanguineous Iraqi family in which affected siblings had mild mental retardation and congenital ataxia characterized by quadrupedal gait. The mutation S100P is associated with proteasome-mediated degradation, and presumably represents a null mutation. (PMID:19461874)
• review article describes the previous data on CARP VIII, including its structure, role in neurodegeneration and cancer; and bioinformatic and expression analyses. (PMID:20819067)
• This report expands the neurological and radiological phenotype associated with CA8 mutations. (PMID:21812104)
• Overexpression of CA8 in MERRF cybrids significantly decreases cell death. (PMID:24476000)
• CA8 overexpression desensitizes neuronal cells to STS induced apoptotic stress and increases cell migration and invasion ability in neuronal cells. (PMID:24794067)
• we observed increased expression of CA8 in more aggressive types of human osteosarcoma (OS) cells and found that CA8 expression is correlated with disease stages, such that more intense expression occurs in the disease late stage (PMID:26711783)
• results suggest that Sp1 transactivates hCA8 gene through the proximal GC box element in the promoter region (PMID:29407793)
• The CARP VIII and XI proteins were associated to non-hypoxic conditions and CARP XI also to the expression of cytoplasmic CA II staining suggesting that the CARPs play a role in tumorigenesis of diffusively infiltrating gliomas. (PMID:29792187)
• These genomic studies significantly advance the literature regarding structure-function studies on CA8-ITPR1 critical to calcium signaling pathways, synaptic functioning, neuronal excitability and analgesic responses. (PMID:31199789)
• Cerebellar ataxia with normal intellect associated with a homozygous truncating variant in CA8. (PMID:31693170)
• CA8 promotes renal cell carcinoma proliferation and migration though its expression level is lower in tumor compared to adjacent normal tissue (PMID:31715371)
• Expression and Functional Study of Single Mutations of Carbonic Anhydrase 8 in Neuronal Cells. (PMID:32583043)
• Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo. (PMID:33247772)
• Altered glucose metabolism and its association with carbonic anhydrase 8 in Machado-Joseph Disease. (PMID:35488942)
• Carbonic anhydrase XII as biomarker and therapeutic target in ovarian carcinomas. (PMID:35901081)
• Effects of down-regulated carbonic anhydrase 8 on cell survival and glucose metabolism in human colorectal cancer cell lines. (PMID:38571370)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	ca8	ENSDARG00000039098
mus_musculus	Car8	ENSMUSG00000041261
rattus_norvegicus	Car8	ENSRNOG00000005669
drosophila_melanogaster	CAH13	FBGN0033542
drosophila_melanogaster	CAH14	FBGN0034554
drosophila_melanogaster	CAH15	FBGN0034560
drosophila_melanogaster	CAH7	FBGN0037788
drosophila_melanogaster	CAH8	FBGN0038956
drosophila_melanogaster	CAH4	FBGN0039235
drosophila_melanogaster	CAH9	FBGN0039486
drosophila_melanogaster	CAH6	FBGN0039838
drosophila_melanogaster	CAH16	FBGN0040628
drosophila_melanogaster	CAH5	FBGN0040629
drosophila_melanogaster	CARPB	FBGN0052698
caenorhabditis_elegans		WBGENE00000279
caenorhabditis_elegans		WBGENE00000283
caenorhabditis_elegans	cah-6	WBGENE00000284

Paralogs (14): CA11 (ENSG00000063180), CA12 (ENSG00000074410), CA2 (ENSG00000104267), CA9 (ENSG00000107159), CA14 (ENSG00000118298), CA6 (ENSG00000131686), CA1 (ENSG00000133742), CA10 (ENSG00000154975), CA3 (ENSG00000164879), CA4 (ENSG00000167434), CA7 (ENSG00000168748), CA5B (ENSG00000169239), CA5A (ENSG00000174990), CA13 (ENSG00000185015)

Protein

Protein identifiers

Carbonic anhydrase-related protein — P35219 (reviewed: P35219)

Alternative names: Carbonic anhydrase VIII

All UniProt accessions (1): P35219

UniProt curated annotations — full annotation on UniProt →

Function. Does not have a carbonic anhydrase catalytic activity.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 34 (SCAR34) [MIM:613227] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR34 is characterized by congenital cerebellar ataxia associated with dysarthia, quadrupedal gait and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the alpha-carbonic anhydrase family.

RefSeq proteins (4): NP_001308766, NP_001308767, NP_001308768, NP_004047* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001148	CA_dom	Domain
IPR018338	Carbonic_anhydrase_a-class_CS	Conserved_site
IPR023561	Carbonic_anhydrase_a-class	Family
IPR036398	CA_dom_sf	Homologous_superfamily
IPR041877	CARP_VIII	Family

Pfam: PF00194

Enzyme classification (BRENDA):

• EC 4.2.1.1 — carbonic anhydrase (BRENDA: 178 organisms, 196 substrates, 2137 inhibitors, 263 Km, 291 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CO2	0.012–4700	194
4-NITROPHENYL ACETATE	0.0024–30.53	16
H2CO3	0.434–112.7	16
HCO3-	9.3–37	4
P-NITROPHENYL ACETATE	3.86–6.8	4
4-NITROPHENYL PHOSPHATE	0.935–2.195	2
COS	1.86	1
HISTAMINE	7.9	1
CS2	—	0

UniProt features (36 total): strand 15, helix 9, binding site 2, chain 1, domain 1, sequence conflict 1, region of interest 1, turn 1, compositionally biased region 1, active site 1, site 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2W2J	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35219-F1	90.51	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 87 (proton donor/acceptor); 116 (ancestral zinc ligand)

Ligand- & substrate-binding residues (2): 118; 141

Post-translational modifications (1): 5

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): GOMF_CARBONATE_DEHYDRATASE_ACTIVITY, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, MODULE_294, MODULE_295, LIU_CMYB_TARGETS_UP, GOMF_HYDRO_LYASE_ACTIVITY, LIU_VMYB_TARGETS_UP, LEE_TARGETS_OF_PTCH1_AND_SUFU_DN, GEORGES_TARGETS_OF_MIR192_AND_MIR215, MATSUDA_NATURAL_KILLER_DIFFERENTIATION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, MODULE_343, chr8q12, SWEET_LUNG_CANCER_KRAS_UP

GO Biological Process (1): positive regulation of calcium-mediated signaling (GO:0050850)

GO Molecular Function (4): carbonate dehydratase activity (GO:0004089), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
hydro-lyase activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1130 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CA8	CYP24A1	Q07973	870
CA8	VLDLR	P98155	864
CA8	ITPR1	Q14643	862
CA8	AHCYL1	O43865	634
CA8	ALB	P02768	561
CA8	TG	P01266	545
CA8	RNASE1	P07998	535
CA8	A0A087WTN9	A0A087WTN9	526
CA8	FTH1	P02794	508
CA8	OPN1LW	P04000	489
CA8	ERP44	Q9BS26	484
CA8	ATRN	O75882	476
CA8	MYCBP2	O75592	471
CA8	HOMER3	Q9NSC5	430
CA8	ZNF236	Q9UL36	416

IntAct

74 interactions, top by confidence:

A	B	Type	Score
HSD17B14	CA8	psi-mi:“MI:0915”(physical association)	0.890
CA8	HSD17B14	psi-mi:“MI:0915”(physical association)	0.890
MAGED1	CA8	psi-mi:“MI:0915”(physical association)	0.810
CA8	MAGED1	psi-mi:“MI:0915”(physical association)	0.810
CA8	CRX	psi-mi:“MI:0915”(physical association)	0.780
CRX	CA8	psi-mi:“MI:0915”(physical association)	0.780
LNX1	CA8	psi-mi:“MI:0915”(physical association)	0.720
CA8	SPDL1	psi-mi:“MI:0915”(physical association)	0.720
CA8	GGA2	psi-mi:“MI:0915”(physical association)	0.720
CA8	LNX1	psi-mi:“MI:0915”(physical association)	0.720
GGA2	CA8	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (85): CRX (Two-hybrid), TBX3 (Two-hybrid), MAGED1 (Two-hybrid), GGA2 (Two-hybrid), HSD17B14 (Two-hybrid), SPDL1 (Two-hybrid), LNX1 (Two-hybrid), KLK7 (Affinity Capture-MS), IGKC (Affinity Capture-MS), ALB (Affinity Capture-MS), IGHG1 (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), IGHG3 (Affinity Capture-MS), CST6 (Affinity Capture-MS), ITPR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A7H0DN92, A0JN41, A7MAQ2, F4HUC4, F4IHR4, F4JIK2, O04846, O43570, O57211, P04195, P08060, P0DO50, P0DSY1, P0DSY2, P10731, P12890, P18761, P18915, P19021, P20508, P23280, P28651, P35219, P48284, P61215, P97467, Q10462, Q18932, Q20781, Q5PPN4, Q5R4U0, Q5TZ24, Q64444, Q68CI2, Q6RZI9, Q75N34, Q75N35, Q84UV8, Q865C0, Q866X6

Diamond homologs: A0A7H0DN92, A0JN41, B8V7P3, O43570, O57211, O70354, O75493, P00915, P00916, P00918, P00919, P00920, P00921, P00922, P04195, P07450, P07451, P07630, P0DSY1, P0DSY2, P14141, P16015, P20508, P23589, P27139, P28651, P35217, P35218, P35219, P43165, P43166, P48282, P61215, P83299, Q18932, Q1LZA1, Q5PPN4, Q5R4U0, Q5R665, Q5S1S4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

102 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	35
Likely benign	7
Benign	36

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
17604	NM_004056.6(CA8):c.298T>C (p.Ser100Pro)	Pathogenic
29620	NM_004056.6(CA8):c.710G>A (p.Arg237Gln)	Pathogenic
3063040	GRCh37/hg19 8q12.1-12.2(chr8:61007747-61901412)x1	Pathogenic
3335814	NM_004056.6(CA8):c.484G>A (p.Gly162Arg)	Pathogenic
3335815	NM_004056.6(CA8):c.232C>T (p.Arg78Ter)	Pathogenic
3335816	NM_004056.6(CA8):c.251A>G (p.Asn84Ser)	Pathogenic
3773813	NM_004056.6(CA8):c.823C>T (p.Arg275Trp)	Likely pathogenic
3897866	NM_004056.6(CA8):c.251A>C (p.Asn84Thr)	Likely pathogenic
522600	NM_004056.6(CA8):c.475A>T (p.Lys159Ter)	Likely pathogenic
560540	NM_004056.6(CA8):c.100+1G>A	Likely pathogenic
931983	NM_004056.6(CA8):c.730dup (p.Gln244fs)	Likely pathogenic

SpliceAI

2674 predictions. Top by Δscore:

Variant	Effect	Δscore
8:60222771:CACG:C	acceptor_gain	1.0000
8:60222773:C:CT	acceptor_gain	1.0000
8:60222779:CA:C	acceptor_gain	1.0000
8:60222780:A:AC	acceptor_gain	1.0000
8:60222780:A:C	acceptor_gain	1.0000
8:60224532:CTCA:C	donor_loss	1.0000
8:60224533:TCA:T	donor_loss	1.0000
8:60224534:CA:C	donor_loss	1.0000
8:60224535:A:T	donor_loss	1.0000
8:60224536:C:CT	donor_loss	1.0000
8:60224581:TTCCC:T	acceptor_gain	1.0000
8:60224582:TCCC:T	acceptor_gain	1.0000
8:60224583:CCC:C	acceptor_gain	1.0000
8:60224583:CCCC:C	acceptor_gain	1.0000
8:60224583:CCCCT:C	acceptor_loss	1.0000
8:60224584:CC:C	acceptor_gain	1.0000
8:60224584:CCC:C	acceptor_gain	1.0000
8:60224585:CC:C	acceptor_gain	1.0000
8:60224586:C:CA	acceptor_loss	1.0000
8:60224586:C:CC	acceptor_gain	1.0000
8:60224587:T:A	acceptor_loss	1.0000
8:60265919:TCTTA:T	donor_loss	1.0000
8:60265920:CTTAC:C	donor_loss	1.0000
8:60265921:TTAC:T	donor_loss	1.0000
8:60265922:TACCT:T	donor_loss	1.0000
8:60265923:ACCT:A	donor_gain	1.0000
8:60265924:C:A	donor_loss	1.0000
8:60265924:CCT:C	donor_gain	1.0000
8:60265924:CCTC:C	donor_gain	1.0000
8:60266045:AAGAA:A	acceptor_gain	1.0000

AlphaMissense

1890 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:60208791:A:C	F289L	0.999
8:60208791:A:T	F289L	0.999
8:60208793:A:G	F289L	0.999
8:60208809:T:A	R283S	0.999
8:60208809:T:G	R283S	0.999
8:60208836:A:C	F274L	0.999
8:60208836:A:T	F274L	0.999
8:60208838:A:G	F274L	0.999
8:60208839:G:C	N273K	0.999
8:60208839:G:T	N273K	0.999
8:60208906:C:G	R251P	0.999
8:60222690:A:G	W233R	0.999
8:60222690:A:T	W233R	0.999
8:60222706:G:C	C227W	0.999
8:60222729:C:G	G220R	0.999
8:60222741:A:G	W216R	0.999
8:60222741:A:T	W216R	0.999
8:60265934:A:C	F136L	0.999
8:60265934:A:T	F136L	0.999
8:60265936:A:G	F136L	0.999
8:60265965:C:T	G126D	0.999
8:60265966:C:G	G126R	0.999
8:60265987:A:G	W119R	0.999
8:60265987:A:T	W119R	0.999
8:60279829:G:T	P51H	0.999
8:60279870:C:A	W37C	0.999
8:60279870:C:G	W37C	0.999
8:60279872:A:G	W37R	0.999
8:60279872:A:T	W37R	0.999
8:60208810:C:G	R283T	0.998

dbSNP variants (sampled 300 via entrez): RS1000007760 (8:60243195 A>G), RS1000022795 (8:60225732 C>G), RS1000023075 (8:60215081 G>A), RS1000026030 (8:60213683 C>T), RS1000030273 (8:60186308 A>G), RS1000047993 (8:60236355 G>A), RS1000064724 (8:60255333 G>A), RS1000104789 (8:60188104 G>A), RS1000189437 (8:60259968 G>A), RS1000198965 (8:60249189 A>G), RS1000244228 (8:60212726 C>A), RS1000253669 (8:60247275 A>G), RS1000298022 (8:60255849 A>G), RS1000333563 (8:60275781 T>C), RS1000370110 (8:60247429 T>C)

Disease associations

OMIM: gene MIM:114815 | disease phenotypes: MIM:613227

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3	Definitive	Autosomal recessive
cerebellar ataxia, intellectual disability, and dysequilibrium	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
cerebellar ataxia	Moderate	AR

Mondo (2): cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 (MONDO:0013188), cerebellar ataxia, intellectual disability, and dysequilibrium (MONDO:0009133)

Orphanet (1): Dysequilibrium syndrome (Orphanet:1766)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000504	Abnormality of vision
HP:0000518	Cataract
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001288	Gait disturbance
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0003202	Skeletal muscle atrophy
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0009878	Cerebellar ataxia associated with quadrupedal gait
HP:0100021	Cerebral palsy
HP:0100022	Abnormality of movement

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000960_8	Cardiac hypertrophy	2.000000e-06
GCST001651_60	Response to amphetamines	4.000000e-06
GCST001762_875	Obesity-related traits	5.000000e-06
GCST001762_932	Obesity-related traits	9.000000e-06
GCST002539_73	Schizophrenia	6.000000e-09
GCST003984_18	Parkinson’s disease	6.000000e-08
GCST003997_21	Myopia	6.000000e-41
GCST004946_143	Schizophrenia	5.000000e-09
GCST006291_133	Spherical equivalent or myopia (age of diagnosis)	2.000000e-39
GCST006291_44	Spherical equivalent or myopia (age of diagnosis)	7.000000e-12
GCST006585_238	Blood protein levels	6.000000e-14
GCST006803_98	Schizophrenia	3.000000e-11
GCST006896_17	Free thyroxine concentration	7.000000e-12
GCST007201_317	Schizophrenia	2.000000e-08
GCST007201_98	Schizophrenia	2.000000e-09
GCST008839_123	Height	2.000000e-09
GCST010002_301	Refractive error	1.000000e-153
GCST010988_296	Adult body size	2.000000e-09
GCST012403_94	High myopia	2.000000e-08
GCST90002384_245	Hemoglobin	1.000000e-10
GCST90002403_631	Red blood cell count	7.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0005116	urinary metabolite measurement
EFO:0004847	age at onset
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567690	Cerebellar Ataxia, Mental Retardation, And Dysequilibrium Syndrome 3 (supp.)
C535731	Dysequilibrium syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, affects expression, affects cotreatment	8
Benzo(a)pyrene	increases methylation, affects expression, decreases methylation, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Aflatoxin B1	increases methylation, decreases expression	2
bisphenol A	decreases expression	1
diethyl phthalate	decreases expression, increases abundance	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
polyhexamethyleneguanidine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
(+)-JQ1 compound	increases expression	1
monoethyl phthalate	decreases expression, increases abundance	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Coal	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Hydralazine	decreases expression, affects cotreatment	1
Lead	affects expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Methylcholanthrene	increases reaction, affects binding	1
Smoke	increases abundance, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1LS	Abcam K-562 CA8 KO	Cancer cell line	Female
CVCL_D2ID	Abcam Raji CA8 KO	Cancer cell line	Male
CVCL_UQ24	Abcam Jurkat CA8 KO	Cancer cell line	Male

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06366230	PHASE1/PHASE2	RECRUITING	Adding Urea to the Final Dialysis Fluid