CALB2

Summary

CALB2 (calbindin 2, HGNC:1435) is a protein-coding gene on chromosome 16q22.2, encoding Calretinin (P22676). Calcium-binding protein involved in calcium homeostasis and signal transduction.

This gene encodes an intracellular calcium-binding protein belonging to the troponin C superfamily. Members of this protein family have six EF-hand domains which bind calcium. This protein plays a role in diverse cellular functions, including message targeting and intracellular calcium buffering. It also functions as a modulator of neuronal excitability, and is a diagnostic marker for some human diseases, including Hirschsprung disease and some cancers. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 794 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1435
Approved symbol	CALB2
Name	calbindin 2
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Aliases	CAL2
Ensembl gene	ENSG00000172137
Ensembl biotype	protein_coding
OMIM	114051
Entrez	794

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000302628, ENST00000349553, ENST00000467817, ENST00000490520, ENST00000562305, ENST00000870349, ENST00000934439, ENST00000959115

RefSeq mRNA: 2 — MANE Select: NM_001740 NM_001740, NM_007088

CCDS: CCDS10899

Canonical transcript exons

ENST00000302628 — 11 exons

Exon	Start	End
ENSE00001149031	71383970	71384025
ENSE00001149053	71374745	71374834
ENSE00001149060	71372153	71372229
ENSE00001713677	71389749	71390433
ENSE00001900083	71358723	71358886
ENSE00002433272	71383367	71383444
ENSE00002452620	71382719	71382775
ENSE00002488272	71384783	71384836
ENSE00002506029	71384339	71384378
ENSE00002517469	71377667	71377747
ENSE00003664240	71385577	71385648

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 98.13.

FANTOM5 (CAGE): breadth broad, TPM avg 16.5133 / max 1635.2222, expressed in 818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154909	16.5133	818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hypothalamus	UBERON:0001898	98.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.85	gold quality
cerebellum	UBERON:0002037	97.36	gold quality
cerebellar cortex	UBERON:0002129	97.35	gold quality
cerebellar hemisphere	UBERON:0002245	97.33	gold quality
omental fat pad	UBERON:0010414	95.35	gold quality
adipose tissue	UBERON:0001013	94.20	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.19	gold quality
right adrenal gland	UBERON:0001233	92.63	gold quality
right adrenal gland cortex	UBERON:0035827	92.31	gold quality
left adrenal gland cortex	UBERON:0035825	91.52	gold quality
temporal lobe	UBERON:0001871	91.38	gold quality
amygdala	UBERON:0001876	91.37	gold quality
left adrenal gland	UBERON:0001234	91.34	gold quality
anterior cingulate cortex	UBERON:0009835	90.86	gold quality
substantia nigra	UBERON:0002038	89.48	gold quality
right frontal lobe	UBERON:0002810	89.05	gold quality
brain	UBERON:0000955	87.45	gold quality
adrenal gland	UBERON:0002369	87.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.95	gold quality
superior frontal gyrus	UBERON:0002661	86.66	gold quality
cerebral cortex	UBERON:0000956	86.20	gold quality
frontal cortex	UBERON:0001870	85.92	gold quality
caudate nucleus	UBERON:0001873	85.92	gold quality
frontal lobe	UBERON:0016525	85.92	gold quality
colonic epithelium	UBERON:0000397	85.70	gold quality
nucleus accumbens	UBERON:0001882	85.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.93	gold quality
thoracic mammary gland	UBERON:0005200	84.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	263.58
E-ANND-3	yes	17.48
E-HCAD-25	yes	10.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2A, TFAP2D

miRNA regulators (miRDB)

42 targeting CALB2, 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-9-5P	100.00	72.28	2361
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-6511B-5P	97.98	65.64	823

Literature-anchored findings (GeneRIF, showing 40)

• a tumor marker for cardiac myxoma (PMID:11642722)
• Two types of calretinin-immunostained terminals were found in the CA1 region. (PMID:12064772)
• AP2-like cis element acts as an enhancer of gene expression in neuronal cells (PMID:12359331)
• E-cadherin and calretinin are sensitive and specific in differential diagnosis of benign and malignant serous effusion specimens. (PMID:15285029)
• Disorders of Sertoli cell differentiation as indicated by calretinin and/or cytokeratin-18 expression contribute to the multifactorial mechanisms underlying spermatogenic failure (PMID:15950053)
• Calretinin-immunoreactive unipolar brush cells are presented in the vermis after the 28th gestational week. At birth, they are presentm in the vestibular lobules. At the birth the number of calretinin-immunoreactive unipolar brush cells increase. (PMID:16289944)
• Calretinin immunostaining provides some insights into the histogenesis of invasive and noninvasive implants in serous borderline tumors of the ovary. (PMID:16415795)
• Cells lining the mesothelial inclusion cysts had CAL2 immunohistochemical reactivity. (PMID:17535091)
• The combinational characterization of calretinin (either by polyclonal or monoclonal antibody), inhibin alpha, and Melan-A expression is of great significance in the differential diagnosis of adrenocortical tumors. (PMID:18091323)
• Mossy cells of nonhuman primates and humans exhibit different expression pattern for calretinin whereas they show similarities in neurochemical content, such as the cocaine and amphetamine-related transcript peptide. (PMID:18189312)
• The SNP513 in human CALB2 may thus be a predictive marker for colon tumors. (PMID:18214032)
• Calretinin is a useful immunohistochemical marker for ameloblastoma and malignant ameloblastoma. (PMID:18223328)
• Calretinin may have a role in the pathogenesis of ameloblastoma. (PMID:18269580)
• The results of this study indicate with no concurrent change in number of calretinin positive neurons of motor cortex patient with multiple sclerosis. (PMID:18297277)
• Immunostaining for calretinin and CD34 is helpful in the diagnosis of endometrial polyp and hyperplasia (PMID:18604736)
• The data of this study suggest that neurodegenerative processes at play in HD affect the expression of Cr and ChAT in the large striatal interneurons without causing their death. (PMID:18801393)
• Calretinin, MLH-1, and CDX2 may help to differentiate medullary carcinoma from poorly differentiated colonic carcinoma of the colon. (PMID:18992917)
• Up-regulation of calretinin contributes to mesothelioma carcinogenesis (PMID:19435792)
• Calretinin plays a crucial role in the modulation of intrinsic neuronal excitability and the induction of long-term potentiation. (PMID:19450707)
• There is limited utility of calretinin in the diagnosis of sex cord stromal tumors of the ovary, in the differential diagnosis of mesothelioma and serous tumors of the ovary, and in the differential diagnosis of Wolffian lesions and endometrial carcinoma. (PMID:19550372)
• Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease. (PMID:19648883)
• The overall density of Calretinin neurons in cerebral cortex was significantly decreased in focal cortical dysplasias. (PMID:19854615)
• identification of two elements that act as butyrate-sensitive repressors in all colon cancer cell lines tested (PMID:19998412)
• Developed a novel and sensitive ELISA for the detection of calretinin in serum, heparin plasma, or EDTA plasma augmented with calcium from mesothelioma patients. (PMID:20509881)
• calretinin-containing cells in the human hippocampus are highly vulnerable, thus inhibition mediated by dendritic inhibitory cells and their synchronization by interneuron-specific interneurons may be impaired in epilepsy. (PMID:20576695)
• Results suggest that following 5-FU treatment in CRC cell lines, CALB2 is involved in apoptosis induction through the intrinsic mitochondrial pathway. This indicates that CALB2 may be an important mediator of 5-FU-induced cell death (PMID:21629658)
• Low calretinin is associated with high neutrophil-to-lymphocyte ratio and malignant mesothelioma. (PMID:22011651)
• Calretinin appears to be a useful marker to distinguish Olfactory neuroblastoma from other small round blue cell tumors (PMID:22020045)
• Data show calbindin (CB)- and tyrosine hydroxylase (TH)-cells were distributed in the three striatal territories, and the density of calretinin (CR) and parvalbumin (PV) interneurons were more abundant in the associative and sensorimotor striatum. (PMID:22272358)
• Immunohistochemical study of calretinin expression in normal skin and cutaneous adnexal proliferations. (PMID:22343111)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• A set of cryosections revealed extensive colocalization of calretinin with vasoactive intestinal peptide in both surviving submucosal perikarya and mucosal nerve fibres in human chagasic submucosa and mucosa. (PMID:22555304)
• This study demonistrated that significant linear regression between calbindin expression and short-term and long-term percent retention of auditory verbal learning test in patients whose epilepsy (PMID:22796338)
• Over-expression of CR reduces huntingtin-caused cytotoxicity in both non-neuronal and neuronal cell models of Huntington’s disease. (PMID:22891683)
• Our results show that different levels of serous ovarian tumor progression are accompanied by changes in the immunohistochemical expression pattern of EpCAM, CD24, and calretinin (PMID:23011824)
• an unexpected role for CR in directly modulating effectors such as Ca(v)2.1, which may have major consequences for Ca(2+) signaling and neuronal excitability. (PMID:23033479)
• Data show that calretinin and CK5/6 were positive in 100 and 64% of mesotheliomas, and 92 and 31% of reactive effusions, respectively, and desmin was negative in all malignant cases and positive in 85% of reactive effusions. (PMID:23075894)
• High Calretinin expression is associated with mesothelioma. (PMID:23595591)
• Calretinin was found in nerve fibrils in all of the fetal colonic samples. Calretinin was expressed in the gut as early as 22 gestational weeks. (PMID:23701779)
• Restricted diffusion of calretinin in cerebellar granule cell dendrites implies Ca(2)-dependent interactions via its EF-hand 5 domain. (PMID:23732647)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	calb2b	ENSDARG00000036344
danio_rerio	calb2a	ENSDARG00000041062
mus_musculus	Calb2	ENSMUSG00000003657
rattus_norvegicus	Calb2	ENSRNOG00000016977
drosophila_melanogaster	Cbp53E	FBGN0004580

Paralogs (2): SCGN (ENSG00000079689), CALB1 (ENSG00000104327)

Protein

Protein identifiers

Calretinin — P22676 (reviewed: P22676)

Alternative names: 29 kDa calbindin

All UniProt accessions (5): P22676, A0A140VK08, A6NER6, H3BMN5, H3BN14

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-binding protein involved in calcium homeostasis and signal transduction. It plays a critical role in buffering intracellular calcium levels and modulating calcium-dependent signaling pathways. Predominantly expressed in specific neuronal populations, influences synaptic plasticity and neuronal excitability, contributing to learning and memory. During embryonic development, it facilitates neuronal differentiation and maturation.

Subcellular location. Synapse. Cell projection. Dendrite.

Tissue specificity. Brain.

Similarity. Belongs to the calbindin family.

RefSeq proteins (2): NP_001731, NP_009019 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR029646	CALB2	Family
IPR051001	Calbindin_Ca-bind	Family

Pfam: PF13405, PF13499

UniProt features (35 total): binding site 25, domain 6, sequence conflict 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22676-F1	77.29	0.01

Functional residue map

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

Ligand- & substrate-binding residues (25): 35; 40; 76; 78; 80; 82; 87; 120; 122; 124; 126; 131 …

Post-translational modifications (1): 214

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 167 (showing top): AP1_01, chr16q22, GOBP_CELL_CELL_SIGNALING, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, MODULE_66, KANG_FLUOROURACIL_RESISTANCE_DN, AP1_Q4_01, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, BACH2_01, MODULE_157, TGANTCA_AP1_C, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_CYTOSOLIC_CALCIUM_ION_CONCENTRATION, AACTTT_UNKNOWN, GOBP_MONOATOMIC_ION_HOMEOSTASIS

GO Biological Process (4): intracellular calcium ion homeostasis (GO:0006874), regulation of synaptic plasticity (GO:0048167), synaptic signaling (GO:0099536), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509)

GO Molecular Function (3): calcium ion binding (GO:0005509), calcium ion binding involved in regulation of presynaptic cytosolic calcium ion concentration (GO:0099534), metal ion binding (GO:0046872)

GO Cellular Component (12): nucleus (GO:0005634), cytosol (GO:0005829), gap junction (GO:0005921), dendrite (GO:0030425), stereocilium (GO:0032420), cuticular plate (GO:0032437), terminal bouton (GO:0043195), dendriole (GO:0044293), synapse (GO:0045202), parallel fiber to Purkinje cell synapse (GO:0098688), cell projection (GO:0042995), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	2
presynapse	2
neuron projection	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
cell-cell signaling	1
regulation of cytosolic calcium ion concentration	1
neuron cellular homeostasis	1
metal ion binding	1
calcium ion binding	1
regulation of presynaptic cytosolic calcium ion concentration	1
presynaptic cytosol	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cell-cell junction	1
dendritic tree	1
stereocilium bundle	1
actin-based cell projection	1
cortical actin cytoskeleton	1
axon terminus	1
dendrite terminus	1
cell junction	1
excitatory synapse	1

Protein interactions and networks

STRING

3872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALB2	PVALB	P20472	966
CALB2	SST	P01166	932
CALB2	NPY	P01303	900
CALB2	SP8	Q8IXZ3	863
CALB2	GAD1	Q99259	803
CALB2	SDF4	Q9BRK5	801
CALB2	DLX1	P56177	794
CALB2	WT1	P19544	791
CALB2	KRT5	P13647	774
CALB2	KRT7	P08729	773
CALB2	TBR1	Q16650	765
CALB2	CHAT	P28329	761
CALB2	LHX6	Q9UPM6	746
CALB2	RBFOX3	A6NFN3	736
CALB2	S100G	P29377	733

IntAct

16 interactions, top by confidence:

A	B	Type	Score
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
TLX3	CALB2	psi-mi:“MI:0915”(physical association)	0.400
NUFIP1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
HAX1	GPM6B	psi-mi:“MI:0914”(association)	0.350
DGUOK	DNM1L	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
HMX2	CALB2	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
TTC9C		psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS), CALB2 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX0, A1L1L6, A4IG32, B1A8Z2, B1H2N3, C7A278, D2HZB0, O88456, P04632, P06813, P07090, P22676, P47728, Q08331, Q0IIL1, Q17QE5, Q1RMX9, Q2HJF8, Q2KI69, Q32L26, Q32LU1, Q3T0E8, Q3ZBY3, Q4R518, Q5PPL2, Q5RDF9, Q5ZM73, Q6NVC5, Q6P6Q9, Q6P8Y1, Q6PHZ8, Q6PIL6, Q8BG51, Q8HYN7, Q8IXI2, Q8R426, Q8VCX5, Q8WWF8, Q99828, Q99MG9

Diamond homologs: A5PJN0, O76038, P04354, P04467, P05937, P07090, P07171, P12658, P22676, P41044, P47728, Q06A97, Q08331, Q0VFG3, Q25088, Q3ZBY3, Q5R4V1, Q5XJX1, Q63ZJ3, Q6R556, Q91WD9, Q9U6D3, D2DGW3, P05939, P20658, P25070, Q11083, Q1A7B1, Q91482, D3GME4, P05941, P47948, P59747, P86741, P86743, Q1A7B2, Q1A7B3, Q3C2C4, O35508, P02615

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

932 predictions. Top by Δscore:

Variant	Effect	Δscore
16:71358867:G:GT	donor_gain	1.0000
16:71358883:GACG:G	donor_gain	1.0000
16:71358884:ACGG:A	donor_loss	1.0000
16:71358887:G:GA	donor_loss	1.0000
16:71358887:G:GG	donor_gain	1.0000
16:71358890:A:AG	donor_gain	1.0000
16:71358891:G:GG	donor_gain	1.0000
16:71374740:CACA:C	acceptor_loss	1.0000
16:71374741:ACAG:A	acceptor_loss	1.0000
16:71374742:CA:C	acceptor_loss	1.0000
16:71374743:A:AC	acceptor_loss	1.0000
16:71374743:A:AG	acceptor_gain	1.0000
16:71374744:G:GG	acceptor_gain	1.0000
16:71374744:GA:G	acceptor_gain	1.0000
16:71374744:GAT:G	acceptor_gain	1.0000
16:71374831:AGAGG:A	donor_loss	1.0000
16:71374832:GAG:G	donor_gain	1.0000
16:71374836:T:A	donor_loss	1.0000
16:71377665:A:AG	acceptor_gain	1.0000
16:71377666:G:GG	acceptor_gain	1.0000
16:71377666:GCT:G	acceptor_gain	1.0000
16:71382713:TTGCA:T	acceptor_loss	1.0000
16:71382714:TGCAG:T	acceptor_loss	1.0000
16:71382715:GCAG:G	acceptor_loss	1.0000
16:71382716:CAGGC:C	acceptor_loss	1.0000
16:71382717:A:AG	acceptor_gain	1.0000
16:71382717:AGGCT:A	acceptor_loss	1.0000
16:71382718:G:A	acceptor_loss	1.0000
16:71382718:G:GG	acceptor_gain	1.0000
16:71382774:AGGT:A	donor_loss	1.0000

AlphaMissense

1818 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:71383979:T:C	F163L	1.000
16:71383981:T:A	F163L	1.000
16:71383981:T:G	F163L	1.000
16:71358865:T:A	W25R	0.999
16:71358865:T:C	W25R	0.999
16:71372165:T:A	I36N	0.999
16:71372180:T:C	L41P	0.999
16:71377668:T:C	L88P	0.999
16:71377680:T:C	L92P	0.999
16:71377697:T:C	F98L	0.999
16:71377699:C:A	F98L	0.999
16:71377699:C:G	F98L	0.999
16:71382722:T:A	W116R	0.999
16:71382722:T:C	W116R	0.999
16:71382756:T:A	I127N	0.999
16:71382771:T:A	L132H	0.999
16:71382771:T:C	L132P	0.999
16:71383374:T:C	L136P	0.999
16:71383383:T:C	L139P	0.999
16:71383386:T:C	L140P	0.999
16:71383971:T:C	L160P	0.999
16:71383983:A:C	D164A	0.999
16:71383983:A:T	D164V	0.999
16:71384004:T:C	L171S	0.999
16:71385608:T:C	L220P	0.999
16:71358853:T:C	F21L	0.998
16:71358854:T:C	F21S	0.998
16:71358855:C:A	F21L	0.998
16:71358855:C:G	F21L	0.998
16:71377698:T:C	F98S	0.998

dbSNP variants (sampled 300 via entrez): RS1000018017 (16:71364986 C>A), RS1000031506 (16:71358951 G>C), RS1000076978 (16:71362715 T>G), RS1000171033 (16:71374145 A>C), RS1000201374 (16:71368235 C>T), RS1000226297 (16:71383263 C>A), RS1000280269 (16:71379937 T>A,C,G), RS1000449278 (16:71377051 C>T), RS1000472632 (16:71360993 G>A), RS1000526579 (16:71365237 C>T), RS1000581835 (16:71379656 A>T), RS1000735598 (16:71376739 CCACA>C,CCA), RS1000853277 (16:71357703 C>T), RS1000874537 (16:71358059 C>T), RS1000876904 (16:71373780 A>C)

Disease associations

OMIM: gene MIM:114051 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006810_25	Self-reported risk-taking behaviour	4.000000e-08
GCST006811_1	Body mass index	4.000000e-10
GCST007323_32	Risk-taking tendency (4-domain principal component model)	2.000000e-08
GCST007325_241	General risk tolerance (MTAG)	2.000000e-09
GCST008357_12	Mood instability	3.000000e-08
GCST012306_1	Bipolar disorder	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0004340	body mass index
EFO:0008475	mood instability measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects methylation, decreases expression, increases expression	5
bisphenol A	decreases expression, increases expression, affects cotreatment	4
Estradiol	increases expression, affects expression	3
Valproic Acid	increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
methylmercuric chloride	increases expression	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression, decreases methylation	2
sotorasib	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
butyraldehyde	increases expression	1
hydroquinone	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
butylparaben	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
licochalcone B	increases expression	1
jinfukang	increases expression	1

Clinical trials (associated diseases)

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