CIBAR1

Summary

CIBAR1 (CBY1 interacting BAR domain containing 1, HGNC:30452) is a protein-coding gene on chromosome 8q22.1, encoding CBY1-interacting BAR domain-containing protein 1 (A1XBS5). Plays a critical role in regulating mitochondrial ultrastructure and function by maintaining the integrity of mitochondrial morphology, particularly the organization of cristae.

Enables phospholipid binding activity. Involved in several processes, including inner mitochondrial membrane organization; limb morphogenesis; and membrane tubulation. Located in several cellular components, including centriole; ciliary base; and mitochondrial crista.

Source: NCBI Gene 137392 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polydactyly, postaxial, type A9 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 48 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_145269

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30452
Approved symbol	CIBAR1
Name	CBY1 interacting BAR domain containing 1
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38979, BARMR1
Ensembl gene	ENSG00000188343
Ensembl biotype	protein_coding
OMIM	617273
Entrez	137392

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000359421, ENST00000423990, ENST00000452913, ENST00000517718, ENST00000518116, ENST00000518322, ENST00000518829, ENST00000519135, ENST00000519679, ENST00000520363, ENST00000520937, ENST00000520955, ENST00000521641, ENST00000522324, ENST00000522803, ENST00000523453, ENST00000523475, ENST00000523577, ENST00000933183, ENST00000933184, ENST00000949630

RefSeq mRNA: 2 — MANE Select: NM_145269 NM_001283034, NM_145269

CCDS: CCDS47892, CCDS64933

Canonical transcript exons

ENST00000518322 — 9 exons

Exon	Start	End
ENSE00002129115	93728205	93731527
ENSE00002137225	93700550	93700673
ENSE00003469908	93703620	93703688
ENSE00003509393	93709771	93709875
ENSE00003530554	93708011	93708016
ENSE00003541357	93718675	93718788
ENSE00003616168	93726394	93726513
ENSE00003686306	93701224	93701458
ENSE00003791450	93704909	93705010

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6430 / max 237.4867, expressed in 1669 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89752	21.1995	1669
89751	0.1704	59
89750	0.1152	32
89753	0.0741	12
89755	0.0498	16
89754	0.0340	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.49	gold quality
right testis	UBERON:0004534	98.37	gold quality
testis	UBERON:0000473	96.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.54	gold quality
adrenal tissue	UBERON:0018303	96.47	gold quality
calcaneal tendon	UBERON:0003701	94.89	gold quality
stromal cell of endometrium	CL:0002255	93.98	gold quality
ganglionic eminence	UBERON:0004023	93.83	gold quality
cortical plate	UBERON:0005343	93.68	gold quality
ventricular zone	UBERON:0003053	93.14	gold quality
anterior cingulate cortex	UBERON:0009835	93.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.97	gold quality
cingulate cortex	UBERON:0003027	92.94	gold quality
right frontal lobe	UBERON:0002810	92.84	gold quality
right adrenal gland cortex	UBERON:0035827	92.79	gold quality
body of pancreas	UBERON:0001150	92.74	gold quality
right adrenal gland	UBERON:0001233	92.58	gold quality
prefrontal cortex	UBERON:0000451	92.43	gold quality
left adrenal gland cortex	UBERON:0035825	92.37	gold quality
left adrenal gland	UBERON:0001234	92.25	gold quality
adenohypophysis	UBERON:0002196	92.17	gold quality
cerebellar hemisphere	UBERON:0002245	91.87	gold quality
right atrium auricular region	UBERON:0006631	91.76	gold quality
cerebellar cortex	UBERON:0002129	91.74	gold quality
right ovary	UBERON:0002118	91.66	gold quality
heart left ventricle	UBERON:0002084	91.62	gold quality
left ovary	UBERON:0002119	91.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.57	gold quality
adrenal gland	UBERON:0002369	91.52	gold quality
adrenal cortex	UBERON:0001235	91.40	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.82
E-CURD-53	no	65.12
E-MTAB-9388	no	8.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting CIBAR1, 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-4713-3P	100.00	65.92	505
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-561-3P	99.64	70.90	3647

Literature-anchored findings (GeneRIF, showing 9)

• FAM92A1 has different splicing variants, and that it may take part in regulating cell proliferation and apoptosis. (PMID:17646714)
• FAM92A1-289 is a new tumor-related gene with oncogenic potentials to probably play roles in renal carcinogenesis. (PMID:19059705)
• FAM92 proteins interact with Cby1 to promote ciliogenesis via regulation of membrane-remodeling processes. (PMID:27528616)
• FAM92A1-289 retains many oncogenic properties evidenced by facilitating cell migration, boosting cell proliferation and promoting colony formation in vitro and tumor growth in vivo, providing evidence for use as as a therapeutic target for cancer treatment. (PMID:27798880)
• a new nonsyndromic autosomal recessive nonsyndromic postaxial polydactyly type A ciliopathy due to a loss-of-function variant in FAM92A. (PMID:30395363)
• The findings uncover a role for a BAR domain FAM92A1 protein as a critical organizer of the mitochondrial ultrastructure that is indispensable for mitochondrial function. (PMID:30404948)
• BARMR1-mediated sorafenib resistance is derived through stem-like property acquisition by activating integrin-FAK signaling pathways. (PMID:32532973)
• BARMR1/FAM92A1, a novel gene encoding BAR domain protein with multi-functions. (PMID:32891772)
• Optimizing purification of the peripheral membrane protein FAM92A1 fused to a modified spidroin tag. (PMID:34648955)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cibar1	ENSDARG00000004436
mus_musculus	Cibar1	ENSMUSG00000028218
rattus_norvegicus	Cibar1	ENSRNOG00000016338
drosophila_melanogaster	Fam92	FBGN0032428

Paralogs (1): CIBAR2 (ENSG00000153789)

Protein

Protein identifiers

CBY1-interacting BAR domain-containing protein 1 — A1XBS5 (reviewed: A1XBS5)

All UniProt accessions (12): A0A0B4J212, A1XBS5, E5RFH7, E5RFS7, E5RGD0, E5RGE3, E5RGP4, E5RHA4, E5RHK0, E5RID3, F8W7P5, H0YC32

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in regulating mitochondrial ultrastructure and function by maintaining the integrity of mitochondrial morphology, particularly the organization of cristae. Preferentially binds to negatively charged phospholipids like cardiolipin and phosphatidylinositol 4,5-bisphosphate enhancing its interaction with mitochondrial membranes. Induces membrane curvature and tubulation, which are critical for maintaining mitochondrial ultrastructure and the organization of cristae. Plays a crucial role in ciliogenesis. May play a role in limb development through its role in ciliogenesis. Plays a key role in the correct positioning of the annulus, a septin-based ring structure in the sperm flagellum, serving both as a physical barrier and a membrane diffusion barrier that separates the midpiece (MP) from the principal piece (PP). This positioning is essential for proper sperm motility and function. Interacts with CBY3 to form a complex which localizes to the curved membrane region of the flagellar pocket. By doing so, may provide stability and rigidity to the periannular membrane to prevent membrane deformation. This function is crucial for halting annulus migration at the proximal end of the fibrous sheath-containing PP.

Subunit / interactions. Homodimer (via BAR-like domain). Heterodimer with FAM92B (via BAR-like domains). Interacts (via BAR-like domain) with CBY1; this interaction is required for targeting FAM92A to centriole and cilium basal body. Interacts (via BAR-like domain) with CBY3; both proteins form a ninefold symmetric structure at the flagellar base; are recruited to the annulus in a mutually dependent manner and regulate annulus positioning.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cilium basal body. Cell projection. Cilium. Nucleus. Mitochondrion inner membrane. Flagellum Nucleus.

Disease relevance. Polydactyly, postaxial, A9 (PAPA9) [MIM:618219] A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA9 is an autosomal recessive condition characterized by one or more posterior or postaxial digits. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The BAR-like domain displays limited similarity to other BAR domains.

Similarity. Belongs to the CIBAR family.

Isoforms (5)

UniProt ID	Names	Canonical?
A1XBS5-1	1, FAM92A1-289	yes
A1XBS5-2	2, FAM92A1-251
A1XBS5-3	3
A1XBS5-4	4
A1XBS5-5	5

RefSeq proteins (2): NP_001269963, NP_660312* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009602	CBAR/FAM92	Family
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR035590	BAR_CBAR1/2	Domain

Pfam: PF06730

UniProt features (37 total): mutagenesis site 15, helix 6, splice variant 5, sequence conflict 3, sequence variant 2, region of interest 2, transit peptide 1, chain 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8CEG	X-RAY DIFFRACTION	2.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1XBS5-F1	85.36	0.72

Functional residue map

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

Mutagenesis-validated functional residues (15):

Position	Phenotype
107	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-109 and a-110
107	abolishes ability to induce membrane remodeling in the presence of cby1; when associated with e-110; e-114; e-132; e-134
109	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-107 and a-110
110	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-107 and a-109
110	abolishes ability to induce membrane remodeling in the presence of cby1; when associated with e-107;e-114; e-132; e-134
114	abolishes ability to induce membrane remodeling in the presence of cby1; when associated with e-107; e-110; e-132; e-134
132	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-134 and a-136
132	abolishes ability to induce membrane remodeling in the presence of cby1; when associated with e-107; e-110; e-114; e-134
134	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-132 and a-136
134	abolishes ability to induce membrane remodeling in the presence of cby1; when associated with e-107; e-110; e-114; e-132
136	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-132 and a-134
136	abolishes ability to induce membrane remodeling in the presence of cby1; when associated with e-107; e-110; e-114; e-132
264	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-266 and a-267
266	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-264 and a-267
267	reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with a-264 and a-266

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, MARTINEZ_RB1_TARGETS_DN, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN, GOBP_CILIUM_ORGANIZATION, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_APPENDAGE_DEVELOPMENT, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANELLE_ASSEMBLY, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, chr8q22, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, GOBP_SMOOTHENED_SIGNALING_PATHWAY

GO Biological Process (9): inner mitochondrial membrane organization (GO:0007007), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), limb morphogenesis (GO:0035108), positive regulation of smoothened signaling pathway (GO:0045880), cilium assembly (GO:0060271), membrane organization (GO:0061024), membrane tubulation (GO:0097749), cell projection organization (GO:0030030)

GO Molecular Function (2): phospholipid binding (GO:0005543), protein binding (GO:0005515)

GO Cellular Component (16): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), centriole (GO:0005814), mitochondrial crista (GO:0030061), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), sperm annulus (GO:0097227), ciliary base (GO:0097546), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
cilium	4
cellular component organization	2
intracellular membrane-bounded organelle	2
microtubule organizing center	2
intracellular membraneless organelle	2
mitochondrial membrane organization	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
appendage morphogenesis	1
limb development	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
positive regulation of signal transduction	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
membrane organization	1
lipid binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial inner membrane	1
sperm flagellum	1
ciliary transition zone	1
ciliary transition fiber	1
microtubule cytoskeleton	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIBAR1	CBY1	Q9Y3M2	772
CIBAR1	VWA8	A3KMH1	600
CIBAR1	DZIP1L	Q8IYY4	596
CIBAR1	KIAA0825	Q8IV33	593
CIBAR1	IQCE	Q6IPM2	591
CIBAR1	ZNF141	Q15928	576
CIBAR1	SCRN1	Q12765	544
CIBAR1	DZIP1	Q86YF9	528
CIBAR1	TTC23	Q5W5X9	514
CIBAR1	TXNDC15	Q96J42	503
CIBAR1	CEP164	Q9UPV0	437
CIBAR1	PRDM16	Q9HAZ2	415
CIBAR1	UBTD2	Q8WUN7	391
CIBAR1	VENTX	O95231	380
CIBAR1	OGFRL1	Q5TC84	374

IntAct

31 interactions, top by confidence:

A	B	Type	Score
CBY1	CIBAR1	psi-mi:“MI:0915”(physical association)	0.670
CIBAR1	CBY1	psi-mi:“MI:0915”(physical association)	0.670
CBY1	CIBAR1	psi-mi:“MI:0914”(association)	0.670
CIBAR1	APPBP2	psi-mi:“MI:0915”(physical association)	0.490
CIBAR1		psi-mi:“MI:0915”(physical association)	0.400
CIBAR1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
COPB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
PAGE1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
LURAP1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MBIP	CIBAR1	psi-mi:“MI:0914”(association)	0.350
HDGFL2	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MCC	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CCDC85A	CIBAR1	psi-mi:“MI:0914”(association)	0.350
PER2	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	MED19	psi-mi:“MI:0914”(association)	0.350
FBLN7	CIBAR1	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MRPS26	CIBAR1	psi-mi:“MI:0914”(association)	0.350
FAM9B	CIBAR1	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	ARHGAP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): FAM92A1 (Two-hybrid), FAM92A1 (Affinity Capture-MS), FAM92A1 (Affinity Capture-MS), FAM92A1 (Affinity Capture-MS), FAM92A1 (Affinity Capture-MS), FAM92A1 (Two-hybrid), FAM92A1 (Two-hybrid), FAM92A1 (Proximity Label-MS), FAM92A1 (Affinity Capture-MS), FAM92A1 (Proximity Label-MS), FAM92A1 (Two-hybrid), FAM92A1 (Affinity Capture-MS), FAM92A1 (Affinity Capture-MS), FAM92A1 (Affinity Capture-MS), FAM92A1 (Affinity Capture-MS)

ESM2 similar proteins: A1XBS5, B0S6J3, D4A208, O35180, O35964, O43295, O75044, P0DJJ0, P0DMP2, P25343, Q08DK5, Q15057, Q1LU86, Q1RMK1, Q2VR06, Q32LM0, Q3SZG6, Q3V2J0, Q5AFE4, Q5FVC7, Q5PPJ9, Q5PPZ5, Q5R8P5, Q5ZIR1, Q5ZJ81, Q5ZK62, Q62419, Q62421, Q68FW8, Q6AYE2, Q6GN09, Q6IVG4, Q6ZQK5, Q6ZTR7, Q7Z6B7, Q812A2, Q8AXU9, Q8BP22, Q8I190, Q8I1C0

Diamond homologs: A1XBS5, Q1LU86, Q1RMK1, Q2VR06, Q3SZG6, Q3V2J0, Q6GN09, Q6ZTR7, Q8BP22, Q9VK91

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	34
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1687560	NM_145269.5(CIBAR1):c.364C>T (p.Arg122Ter)	Pathogenic
592165	NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter)	Pathogenic
2442170	NM_145269.5(CIBAR1):c.394_397del (p.Arg132fs)	Likely pathogenic

SpliceAI

1321 predictions. Top by Δscore:

Variant	Effect	Δscore
8:93701207:T:TA	acceptor_gain	1.0000
8:93701211:A:AG	acceptor_gain	1.0000
8:93701212:C:G	acceptor_gain	1.0000
8:93701220:CTAG:C	acceptor_loss	1.0000
8:93701222:A:AG	acceptor_gain	1.0000
8:93701222:AG:A	acceptor_gain	1.0000
8:93701223:G:A	acceptor_gain	1.0000
8:93701223:G:GG	acceptor_gain	1.0000
8:93701223:GGA:G	acceptor_gain	1.0000
8:93701223:GGAA:G	acceptor_gain	1.0000
8:93701223:GGAAC:G	acceptor_gain	1.0000
8:93701421:A:G	donor_gain	1.0000
8:93701454:CAGAG:C	donor_loss	1.0000
8:93701455:AGAG:A	donor_loss	1.0000
8:93701456:GAG:G	donor_gain	1.0000
8:93701458:GGTAT:G	donor_loss	1.0000
8:93701459:G:GC	donor_loss	1.0000
8:93701460:T:G	donor_loss	1.0000
8:93703615:A:AG	acceptor_gain	1.0000
8:93703615:AATAG:A	acceptor_gain	1.0000
8:93703616:A:G	acceptor_gain	1.0000
8:93703618:A:AG	acceptor_gain	1.0000
8:93703618:AGGT:A	acceptor_loss	1.0000
8:93703619:G:GA	acceptor_gain	1.0000
8:93703619:GGTT:G	acceptor_gain	1.0000
8:93703684:AACGG:A	donor_gain	1.0000
8:93703685:ACGG:A	donor_gain	1.0000
8:93703686:CGGG:C	donor_loss	1.0000
8:93703687:GG:G	donor_gain	1.0000
8:93703688:GG:G	donor_gain	1.0000

AlphaMissense

1882 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:93701331:G:C	R45T	1.000
8:93701331:G:T	R45I	1.000
8:93701332:A:C	R45S	1.000
8:93701332:A:T	R45S	1.000
8:93701448:G:C	R84P	1.000
8:93701322:C:A	A42D	0.999
8:93701328:T:C	L44P	0.999
8:93701334:A:C	D46A	0.999
8:93701339:G:C	A48P	0.999
8:93701406:T:C	L70P	0.999
8:93701453:G:C	A86P	0.999
8:93703630:T:C	L91P	0.999
8:93703654:T:C	L99S	0.999
8:93718723:G:C	A198P	0.999
8:93718744:G:C	A205P	0.999
8:93701286:T:C	L30P	0.998
8:93701333:G:C	D46H	0.998
8:93701349:T:C	L51P	0.998
8:93701372:G:C	A59P	0.998
8:93701417:G:C	A74P	0.998
8:93718690:T:C	F187L	0.998
8:93718692:T:A	F187L	0.998
8:93718692:T:G	F187L	0.998
8:93718745:C:A	A205D	0.998
8:93701301:C:A	A35D	0.997
8:93701313:G:C	R39P	0.997
8:93701334:A:T	D46V	0.997
8:93701335:C:A	D46E	0.997
8:93701335:C:G	D46E	0.997
8:93701342:G:C	D49H	0.997

dbSNP variants (sampled 300 via entrez): RS1000012792 (8:93731513 A>C), RS1000162151 (8:93715353 C>A,T), RS1000342649 (8:93720525 C>T), RS1000400155 (8:93727126 A>G), RS1000514042 (8:93714296 G>A), RS1000518147 (8:93702209 A>G,T), RS1000621024 (8:93707002 C>A,T), RS1000786070 (8:93700981 A>G), RS1000855631 (8:93726716 T>G), RS1000924577 (8:93714106 T>A), RS1001045069 (8:93720472 AT>A), RS1001115315 (8:93721252 AT>A), RS1001119992 (8:93700763 C>T), RS1001148589 (8:93706661 A>G), RS1001202526 (8:93706419 T>G)

Disease associations

OMIM: gene MIM:617273 | disease phenotypes: MIM:618219

GenCC curated gene-disease

Disease	Classification	Inheritance
polydactyly, postaxial, type A9	Moderate	Autosomal recessive
postaxial polydactyly type A	Supportive	Autosomal recessive

Mondo (2): polydactyly, postaxial, type A9 (MONDO:0032603), postaxial polydactyly type A (MONDO:0019673)

Orphanet (1): Postaxial polydactyly type A (Orphanet:93334)

HPO phenotypes

3 total (4 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001162	Postaxial hand polydactyly
HP:0001830	Postaxial foot polydactyly
HP:0005696	Postaxial polydactyly type A

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001531_8	Temperament	3.000000e-06
GCST006994_2	Logical memory (immediate recall) in Alzheimer’s disease dementia	4.000000e-07
GCST007626_6	Lack of perseverance	7.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004825	temperament and character inventory
EFO:0004874	memory performance
EFO:0006946	behavioural disinhibition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects cotreatment, increases abundance, increases expression, affects methylation	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
kojic acid	increases expression	1
methylparaben	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Diethylstilbestrol	decreases expression	1
Gallic Acid	decreases expression	1
Ketoconazole	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Mercuric Chloride	decreases expression	1
Silicon Dioxide	increases expression	1
Thimerosal	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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