CALB1

Summary

CALB1 (calbindin 1, HGNC:1434) is a protein-coding gene on chromosome 8q21.3, encoding Calbindin (P05937). Buffers cytosolic calcium.

The protein encoded by this gene is a member of the calcium-binding protein superfamily that includes calmodulin and troponin C. Originally described as a 27 kDa protein, it is now known to be a 28 kDa protein. It contains four active calcium-binding domains, and has two modified domains that are thought to have lost their calcium binding capability. This protein is thought to buffer entry of calcium upon stimulation of glutamate receptors. Depletion of this protein was noted in patients with Huntington disease.

Source: NCBI Gene 793 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_004929

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1434
Approved symbol	CALB1
Name	calbindin 1
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104327
Ensembl biotype	protein_coding
OMIM	114050
Entrez	793

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 6 retained_intron

ENST00000265431, ENST00000469032, ENST00000473670, ENST00000476853, ENST00000482702, ENST00000497376, ENST00000514406, ENST00000518457, ENST00000520613, ENST00000522070, ENST00000523716, ENST00000892430, ENST00000892431, ENST00000920117

RefSeq mRNA: 2 — MANE Select: NM_004929 NM_001366795, NM_004929

CCDS: CCDS6251

Canonical transcript exons

ENST00000265431 — 11 exons

Exon	Start	End
ENSE00000699388	90063100	90063153
ENSE00000699457	90063406	90063461
ENSE00000699507	90065898	90065975
ENSE00000699519	90068998	90069054
ENSE00001087859	90060629	90060700
ENSE00001228561	90082619	90082879
ENSE00003535146	90058608	90060286
ENSE00003538570	90063281	90063320
ENSE00003543877	90078373	90078447
ENSE00003551111	90082026	90082102
ENSE00003622235	90069154	90069237

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 98.53.

FANTOM5 (CAGE): breadth broad, TPM avg 7.7816 / max 914.7671, expressed in 354 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93882	7.7695	350
93883	0.0085	5
205250	0.0037	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nephron tubule	UBERON:0001231	98.53	gold quality
cerebellar vermis	UBERON:0004720	97.52	gold quality
kidney epithelium	UBERON:0004819	96.64	gold quality
adult mammalian kidney	UBERON:0000082	96.39	gold quality
nucleus accumbens	UBERON:0001882	95.37	gold quality
renal glomerulus	UBERON:0000074	94.60	gold quality
kidney	UBERON:0002113	94.02	gold quality
metanephric glomerulus	UBERON:0004736	93.84	gold quality
caudate nucleus	UBERON:0001873	93.36	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.25	gold quality
renal medulla	UBERON:0000362	93.22	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.96	gold quality
putamen	UBERON:0001874	91.59	gold quality
adult organism	UBERON:0007023	91.33	gold quality
cerebellum	UBERON:0002037	90.40	gold quality
hypothalamus	UBERON:0001898	90.28	gold quality
orbitofrontal cortex	UBERON:0004167	90.28	gold quality
cerebellar cortex	UBERON:0002129	89.92	gold quality
cerebellar hemisphere	UBERON:0002245	89.70	gold quality
middle temporal gyrus	UBERON:0002771	89.44	gold quality
endothelial cell	CL:0000115	88.94	gold quality
lateral globus pallidus	UBERON:0002476	88.46	gold quality
metanephros	UBERON:0000081	88.40	gold quality
pons	UBERON:0000988	87.73	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.11	gold quality
cortex of kidney	UBERON:0001225	86.56	gold quality
secondary oocyte	CL:0000655	86.04	gold quality
superior frontal gyrus	UBERON:0002661	84.28	gold quality
paraflocculus	UBERON:0005351	83.81	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	1539.59
E-MTAB-6108	yes	641.67
E-MTAB-9388	yes	220.89
E-CURD-119	yes	34.13
E-MTAB-5061	yes	9.31
E-GEOD-81608	yes	8.87
E-ANND-3	yes	5.15
E-ENAD-27	yes	4.83
E-HCAD-31	yes	4.54
E-GEOD-83139	yes	3.97
E-CURD-135	no	979.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, ESR1, REST, SLC24A3, VDR

miRNA regulators (miRDB)

119 targeting CALB1, 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-4262	100.00	73.26	3931
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4282	99.99	75.36	6408
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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 33)

• S-nitrosation of Ca(2+)-loaded and Ca(2+)-free recombinant calbindin D(28K) from human brain. (PMID:11994015)
• binds to myo-inositol-1(or 4)-monophosphatase (IMPase) and increases the phosphatase activity (PMID:12176979)
• calbindin 1, 28kDa may play a role in Ca2+ transport or cell development in human trophoblast possibly trough Ca2+ buffering (PMID:12606474)
• The biological function of calbindin D28k appears to be tied to the redox state of its five cysteine residues. (PMID:15641794)
• Post-translational modifications of human calbindin. (PMID:15741335)
• Our findings indicate that the expression of parvalbumin or calbindin-D(28k) by subpopulations of dysplastic neurons in cortical tubers is aberrant and denotes dysfunctional inhibitory circuits inept for excitoprotection. (PMID:17156698)
• aggregates of mutant ataxin-l may recruit calbindin-D28k via tissue transglutaminase 2 mediated covalent crosslinking (PMID:17442486)
• recombinant human calbindin-D28k was crystallized at 291 K using PEG 3350 as precipitant and a 2.4 A resolution X-ray data set was collected from a single flash-cooled crystal (PMID:18259068)
• calbindin D(28k) binds Zn2+ to 3 rather strong sites with dissociation constants in low micromolar range. Zn2+-bound state is structurally distinct from Ca2+-bound state, with negative allosteric interaction between Zn- & Ca-binding events. (PMID:18359862)
• CALB1 is associated with Parkinson’s disease independently of alpha-synuclein. (PMID:18568448)
• No significant differences in cerebellar Purkinje cells in levels of CALB in autism or in the normal cerebellum. (PMID:18587625)
• Our study shows there is no association between rs1805874 and risk for Parkinson’s disease (PD) in four Caucasian populations. This suggests the effect of calbindin on PD risk displays population specificity. (PMID:19674066)
• calbindin may play a role in development of Purkinje cells located in heterotopias and cerebellar dysgenesias (PMID:20054781)
• cultured syncytiotrophoblast cells express calbindin-D9k and calbindin-D28k genes, which are stimulated by calcitriol (PMID:20214988)
• upregulated in endometriosis tissues (PMID:20452033)
• Dynamics of Ca2+ ions within the solvation shell of calbindin D9k. (PMID:21364983)
• 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)
• Significantly reduced hippocampal calbindin D28K levels are found in all patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like syndrome (MELAS). (PMID:22483853)
• The calbindin-D 28k was decreased in the putamen, the dorsal tier of the substantia nigra along the lower border of the red nucleus, and in the cerebellar cortex in multiple system atrophy. (PMID:23715974)
• expressed by different neuron types, both inhibitory (GABAergic) and excitatory (glutamatergic), involved in both intrinsic and extrinsic circuits of the human cerebellar cortex (PMID:24719368)
• Increased number of calbindin neurons and fiber labeling both in focal cortical dysplasia (FCD) and non-FCD specimens compared with postmortem controls may be associated with ongoing seizure activity. (PMID:26081613)
• Age-related loss of CB appears to coincide with tangle formation in the BFCN and is associated with the full range of tau pathology, including late appearing epitopes. (PMID:26417681)
• CSF calbindin concentration is a sensitive biomarker of NPC1 disease (PMID:27307499)
• We identified a significant association between the A allele of rs1805874 and the risk of Parkinson’s disease (OR 1.257, 95% CI 1.036-1.524, p = 0.020). Our findings suggest that the A allele of rs1805874 is associated with risk of Parkinson’s disease among the Han Chinese. Our results, combined with previous studies, suggest that rs1805874 is associated with Parkinson’s disease in East Asians, but not Caucasians. (PMID:27611799)
• SAXS data collected in both the presence and absence of calcium indicate that there are no large structural differences in the globular structure of calbindin-D28K between the calcium-loaded and unloaded proteins. (PMID:30289411)
• the Calreticulin deficiency-mediated increase in cell death was not prevented by calbindin-D28k or Parvalbumin. (PMID:30545133)
• Results suggest that CALB1 is a direct target of miR-454-3p and downregulation of CALB1 by miR-454-3p suppressed NSCLC cell functions. (PMID:30638403)
• Knockdown of CALB1 inhibited the proliferation and colony formation of ovarian cancer cells. CALB1 interacts with MDM2 protooncogene (MDM2) and promoted the interaction between p53 and MDM2. (PMID:31059057)
• Advanced glycation end-products (AGEs) induced the calbindin-D28k expression in human renal proximal tubule cells (HK2), but not in mesangial cells. AGEs induced the expression of fibrotic molecules and endoplasmic reticulum (ER) stress-related molecules in HK2 cells, which could be inhibited by a receptor for AGE neutralizing antibody. (PMID:31262060)
• Protective effects of calbindinD28K on the UVB radiationinduced apoptosis of human lens epithelial cells. (PMID:32236567)
• Brain CHID1 Expression Correlates with NRGN and CALB1 in Healthy Subjects and AD Patients. (PMID:33924468)
• Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular Ca(2+) Levels in Senescent Cells. (PMID:36012633)
• Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin. (PMID:37192000)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	calb1	ENSDARG00000031598
mus_musculus	Calb1	ENSMUSG00000028222
rattus_norvegicus	Calb1	ENSRNOG00000007456
drosophila_melanogaster	Cbp53E	FBGN0004580

Paralogs (2): SCGN (ENSG00000079689), CALB2 (ENSG00000172137)

Protein

Protein identifiers

Calbindin — P05937 (reviewed: P05937)

Alternative names: Calbindin D28, D-28K, Vitamin D-dependent calcium-binding protein, avian-type

All UniProt accessions (3): E5RG14, E5RIZ8, P05937

UniProt curated annotations — full annotation on UniProt →

Function. Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3’,5’-cyclic nucleotide phosphodiesterase.

Subunit / interactions. Interacts with RANBP9.

Domain organisation. This protein has four functional calcium-binding sites; potential sites II and VI have lost affinity for calcium.

Similarity. Belongs to the calbindin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P05937-1	1	yes
P05937-2	2

RefSeq proteins (2): NP_001353724, NP_004920* (*=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
IPR029634	Calbindin_six-EFh_dom	Domain
IPR051001	Calbindin_Ca-bind	Family

Pfam: PF00036, PF13499

Enzyme classification (BRENDA):

• EC 3.1.3.25 — inositol-phosphate phosphatase (BRENDA: 28 organisms, 184 substrates, 148 inhibitors, 96 Km, 55 kcat entries)

Substrate kinetics (BRENDA)

34 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-MYO-INOSITOL 1-PHOSPHATE	0.06–1.02	14
DL-MYO-INOSITOL 1-PHOSPHATE	0.0034–1.67	12
L-MYO-INOSITOL 1-PHOSPHATE	0.061–13.2	8
MYO-INOSITOL 1-PHOSPHATE	0.064–66	8
GLYCEROL 2-PHOSPHATE	0.061–4.17	6
2’-AMP	0.083–1.58	5
4-NITROPHENYL PHOSPHATE	3.8–5	3
D-INOSITOL 1-PHOSPHATE	0.078–0.148	3
L-GLYCEROL 1-PHOSPHATE	0.382–0.87	3
3,5-DIDEOXY-D-MYO-INOSITOL 1-PHOSPHATE	0.051–0.16	2
3,5-DIDEOXY-L-MYO-INOSITOL 1-PHOSPHATE	0.1–4.9	2
3-DEOXY-D-MYO-INOSITOL 1-PHOSPHATE	0.047–0.23	2
3-DEOXY-L-MYO-INOSITOL 1-PHOSPHATE	0.2–2.3	2
D-MYO-INOSITOL 3-PHOSPHATE	0.061–1.7	2
INOSITOL 2-PHOSPHATE	0.286–0.733	2

UniProt features (53 total): binding site 19, helix 17, domain 5, strand 5, turn 2, initiator methionine 1, chain 1, modified residue 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6FIE	X-RAY DIFFRACTION	1.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05937-F1	82.70	0.10

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 (19): 28; 30; 35; 111; 113; 115; 122; 155; 157; 159; 161; 166 …

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-977225	Amyloid fiber formation
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 252 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_MEMORY, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, DORSAM_HOXA9_TARGETS_UP, GOBP_METANEPHROS_DEVELOPMENT, GOBP_METANEPHRIC_EPITHELIUM_DEVELOPMENT, GOBP_NEURAL_RETINA_DEVELOPMENT, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, MODULE_66, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EAR_DEVELOPMENT

GO Biological Process (16): short-term memory (GO:0007614), long-term memory (GO:0007616), locomotory behavior (GO:0007626), retina layer formation (GO:0010842), response to auditory stimulus (GO:0010996), metanephric part of ureteric bud development (GO:0035502), regulation of synaptic plasticity (GO:0048167), metanephric collecting duct development (GO:0072205), metanephric distal convoluted tubule development (GO:0072221), metanephric connecting tubule development (GO:0072286), cochlea development (GO:0090102), learning or memory (GO:0007611), calcium ion homeostasis (GO:0055074), retina development in camera-type eye (GO:0060041), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509), regulation of postsynaptic cytosolic calcium ion concentration (GO:0099566)

GO Molecular Function (7): vitamin D binding (GO:0005499), calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), calcium ion binding involved in regulation of presynaptic cytosolic calcium ion concentration (GO:0099534), calcium ion binding involved in regulation of postsynaptic cytosolic calcium ion concentration (GO:0099567), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (19): nucleus (GO:0005634), cytosol (GO:0005829), axon (GO:0030424), dendrite (GO:0030425), stereocilium (GO:0032420), cuticular plate (GO:0032437), neuronal cell body (GO:0043025), terminal bouton (GO:0043195), calyx of Held (GO:0044305), synapse (GO:0045202), extracellular exosome (GO:0070062), hippocampal mossy fiber to CA3 synapse (GO:0098686), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), presynaptic cytosol (GO:0099523), postsynaptic cytosol (GO:0099524), cytoplasm (GO:0005737), neuron projection (GO:0043005), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
presynapse	3
neuron projection	3
synapse	3
memory	2
behavior	2
metanephric nephron tubule development	2
anatomical structure development	2
regulation of cytosolic calcium ion concentration	2
postsynapse	2
calcium ion binding	2
axon terminus	2
cytosol	2
neural retina development	1
anatomical structure formation involved in morphogenesis	1
retina morphogenesis in camera-type eye	1
response to mechanical stimulus	1
ureteric bud development	1
metanephros morphogenesis	1
tube development	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
metanephros development	1
collecting duct development	1
distal convoluted tubule development	1
metanephric distal tubule development	1
connecting tubule development	1
inner ear development	1
cognition	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
camera-type eye development	1
neuron cellular homeostasis	1
steroid binding	1
vitamin binding	1
metal ion binding	1
transition metal ion binding	1
regulation of presynaptic cytosolic calcium ion concentration	1
presynaptic cytosol	1
postsynaptic cytosol	1

Protein interactions and networks

STRING

4108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALB1	S100G	P29377	969
CALB1	PVALB	P20472	963
CALB1	SDF4	Q9BRK5	884
CALB1	SST	P01166	876
CALB1	GAD1	Q99259	854
CALB1	OSGIN2	Q9Y236	833
CALB1	DECR1	Q16698	831
CALB1	RBFOX3	A6NFN3	786
CALB1	TH	P07101	779
CALB1	NPY	P01303	760
CALB1	S100B	P04271	756
CALB1	GFAP	P14136	749
CALB1	SYP	P08247	739
CALB1	CHAT	P28329	728
CALB1	S100A6	P06703	720

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CALB1	IKBKG	psi-mi:“MI:0915”(physical association)	0.630
BOD1	CALB1	psi-mi:“MI:0915”(physical association)	0.560
CALB1	TRPV5	psi-mi:“MI:0403”(colocalization)	0.460
CALB1	TRPV5	psi-mi:“MI:0915”(physical association)	0.460
TRPV5	CALB1	psi-mi:“MI:0915”(physical association)	0.460
CALB1	CASP3	psi-mi:“MI:0407”(direct interaction)	0.440
CALB1	TRPV6	psi-mi:“MI:0915”(physical association)	0.400
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
GRIPAP1	USO1	psi-mi:“MI:0914”(association)	0.350
IKBKG	CALB1	psi-mi:“MI:0407”(direct interaction)	0.000

BioGRID (11): RANBP9 (Two-hybrid), RANBP9 (Reconstituted Complex), IMPA1 (Protein-peptide), CALB1 (Affinity Capture-MS), CALB1 (Affinity Capture-MS), CALB1 (Affinity Capture-MS), CALB1 (Reconstituted Complex), CALB1 (Affinity Capture-Western), CALB1 (Two-hybrid), CACNA1D (Reconstituted Complex), CALB1 (Affinity Capture-MS)

ESM2 similar proteins: A0AVX7, A2VEI2, F4J0W4, O43745, O70200, O73761, O73762, P04354, P04467, P05937, P07171, P12658, P22728, P41044, P43080, P43081, P46065, P51177, P55008, P61022, P61023, P79880, P81076, Q0V9B1, Q1LWZ0, Q298L5, Q3KQ77, Q3SYS6, Q3T024, Q4R760, Q4V7T8, Q5R4V1, Q5R7F0, Q5TM25, Q5U554, Q5ZM44, Q6P8Y1, Q810D1, Q8IMX7, Q8R426

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

967 predictions. Top by Δscore:

Variant	Effect	Δscore
8:90060697:CGTC:C	acceptor_gain	1.0000
8:90060701:C:CC	acceptor_gain	1.0000
8:90063150:TTCCC:T	acceptor_loss	1.0000
8:90063151:TCCC:T	acceptor_loss	1.0000
8:90063152:CC:C	acceptor_gain	1.0000
8:90063153:CC:C	acceptor_gain	1.0000
8:90063153:CCTA:C	acceptor_loss	1.0000
8:90063154:C:CC	acceptor_gain	1.0000
8:90063154:CTAA:C	acceptor_loss	1.0000
8:90065892:TCTTA:T	donor_loss	1.0000
8:90065893:CTTAC:C	donor_loss	1.0000
8:90065894:TTACC:T	donor_loss	1.0000
8:90065895:TACC:T	donor_loss	1.0000
8:90065971:AAGTT:A	acceptor_gain	1.0000
8:90065972:AGTT:A	acceptor_gain	1.0000
8:90065973:GTT:G	acceptor_gain	1.0000
8:90065974:TT:T	acceptor_gain	1.0000
8:90065974:TTC:T	acceptor_loss	1.0000
8:90065975:TCT:T	acceptor_loss	1.0000
8:90065976:C:CC	acceptor_gain	1.0000
8:90065976:C:T	acceptor_loss	1.0000
8:90065977:T:A	acceptor_loss	1.0000
8:90069067:T:C	acceptor_gain	1.0000
8:90069067:T:TC	acceptor_gain	1.0000
8:90069249:T:C	acceptor_gain	1.0000
8:90078367:CCTTA:C	donor_loss	1.0000
8:90078368:CTT:C	donor_loss	1.0000
8:90078369:TTA:T	donor_loss	1.0000
8:90078370:T:TA	donor_loss	1.0000
8:90078371:A:AT	donor_loss	1.0000

AlphaMissense

1729 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:90069002:A:G	L123P	0.999
8:90069051:A:G	W107R	0.999
8:90069051:A:T	W107R	0.999
8:90060204:A:G	L252P	0.998
8:90060669:A:G	L211P	0.998
8:90063427:A:G	L162P	0.998
8:90069038:T:G	D111A	0.998
8:90069049:C:A	W107C	0.998
8:90069049:C:G	W107C	0.998
8:90060657:A:G	L215P	0.997
8:90063427:A:T	L162Q	0.997
8:90065968:A:G	L127P	0.997
8:90069038:T:A	D111V	0.997
8:90069039:C:G	D111H	0.997
8:90060648:A:G	L218P	0.996
8:90063450:A:C	F154L	0.996
8:90063450:A:T	F154L	0.996
8:90063452:A:G	F154L	0.996
8:90065959:A:G	L130P	0.996
8:90069037:A:C	D111E	0.996
8:90069037:A:T	D111E	0.996
8:90069050:C:G	W107S	0.996
8:90069161:A:G	F103S	0.996
8:90082054:A:G	L43P	0.996
8:90060204:A:T	L252H	0.995
8:90063115:A:C	F195L	0.995
8:90063115:A:T	F195L	0.995
8:90063117:A:G	F195L	0.995
8:90063410:C:G	A168P	0.995
8:90063415:T:A	E166V	0.995

dbSNP variants (sampled 300 via entrez): RS1000105954 (8:90070645 G>A), RS1000139972 (8:90084179 A>C), RS1000232194 (8:90061108 A>C,G), RS1000249 (8:90060266 A>G), RS1000291553 (8:90068044 G>T), RS1000397837 (8:90062508 A>G), RS1000434924 (8:90083824 T>C), RS1000510311 (8:90064671 G>C,T), RS1000791450 (8:90072249 A>G), RS1000857605 (8:90070869 T>A,C), RS1001080060 (8:90071989 G>A), RS1001242933 (8:90067297 T>G), RS1001305728 (8:90062393 G>A), RS1001494629 (8:90078596 G>A,C), RS1001651611 (8:90078916 G>A)

Disease associations

OMIM: gene MIM:114050 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003837_11	Chronotype	2.000000e-08
GCST003838_10	Morning vs. evening chronotype	3.000000e-08
GCST007576_207	Chronotype	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
fluxapyroxad	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
diethanolamine	increases expression	1
cadmium sulfate	increases expression	1
seocalcitol	increases expression	1
CGP 52608	affects binding, increases reaction	1
ZK159222	decreases reaction, increases expression	1
vandetanib	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
belinostat	increases expression	1
abrine	increases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, decreases reaction	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Cisplatin	increases expression	1
Cycloheximide	decreases expression, decreases reaction	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Deoxycholic Acid	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SG56	HAP1 CALB1 (-) 1	Cancer cell line	Male
CVCL_XM43	HAP1 CALB1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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