PDXP

Summary

PDXP (pyridoxal phosphatase, HGNC:30259) is a protein-coding gene on chromosome 22q13.1, encoding Chronophin (Q96GD0). Functions as a pyridoxal phosphate (PLP) phosphatase, which also catalyzes the dephosphorylation of pyridoxine 5’-phosphate (PNP) and pyridoxamine 5’-phosphate (PMP), with order of substrate preference PLP > PNP > PMP and therefore plays a role in vitamin B6 metabolism.

Pyridoxal 5-prime-phosphate (PLP) is the active form of vitamin B6 that acts as a coenzyme in maintaining biochemical homeostasis. The preferred degradation route from PLP to 4-pyridoxic acid involves the dephosphorylation of PLP by PDXP (Jang et al., 2003 [PubMed 14522954]).

Source: NCBI Gene 57026 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_020315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30259
Approved symbol	PDXP
Name	pyridoxal phosphatase
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ37E16.5, FLJ32703, CIN
Ensembl gene	ENSG00000241360
Ensembl biotype	protein_coding
OMIM	609246
Entrez	57026

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000215904, ENST00000403251

RefSeq mRNA: 1 — MANE Select: NM_020315 NM_020315

CCDS: CCDS13953

Canonical transcript exons

ENST00000215904 — 2 exons

Exon	Start	End
ENSE00003992750	37658723	37659356
ENSE00003992754	37665555	37666932

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6692 / max 156.2321, expressed in 1696 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192166	5.3120	1465
192165	4.9101	1489
192167	0.2986	104
192168	0.1485	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.83	gold quality
superior frontal gyrus	UBERON:0002661	98.75	gold quality
frontal cortex	UBERON:0001870	98.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.56	gold quality
primary visual cortex	UBERON:0002436	98.53	gold quality
prefrontal cortex	UBERON:0000451	98.50	gold quality
anterior cingulate cortex	UBERON:0009835	98.40	gold quality
cerebral cortex	UBERON:0000956	98.34	gold quality
temporal lobe	UBERON:0001871	98.31	gold quality
amygdala	UBERON:0001876	98.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.24	gold quality
Ammon’s horn	UBERON:0001954	98.00	gold quality
nucleus accumbens	UBERON:0001882	97.91	gold quality
hypothalamus	UBERON:0001898	97.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.55	gold quality
cerebellum	UBERON:0002037	97.39	gold quality
cerebellar cortex	UBERON:0002129	97.38	gold quality
cerebellar hemisphere	UBERON:0002245	97.37	gold quality
putamen	UBERON:0001874	97.11	gold quality
brain	UBERON:0000955	96.98	gold quality
caudate nucleus	UBERON:0001873	96.95	gold quality
cortical plate	UBERON:0005343	95.52	gold quality
substantia nigra	UBERON:0002038	94.76	gold quality
right lobe of liver	UBERON:0001114	93.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.53	gold quality
mucosa of transverse colon	UBERON:0004991	92.95	gold quality
embryo	UBERON:0000922	92.81	gold quality
ganglionic eminence	UBERON:0004023	92.81	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.60	gold quality
liver	UBERON:0002107	91.45	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

40 targeting PDXP, 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-5692A	100.00	74.40	6850
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-4518	98.12	66.82	1030

Literature-anchored findings (GeneRIF, showing 8)

• analysis of pyridoxal phosphatase cloning, expression and tissue distribution (PMID:14522954)
• We report the biochemical isolation of chronophin (CIN), a unique cofilin-activating phosphatase of the haloacid dehalogenase (HAD) superfamily and an important novel regulator of cofilin-mediated actin reorganization. (PMID:15580268)
• analysis of brain pyridoxal-5’-phosphate phosphatase (PMID:16336786)
• Results suggest that the transduction of the PEP-1-PLPP fusion protein can be one mode of PLP level regulation, and to replenish this enzyme in the various neurological disorders related to vitamin B(6). (PMID:18510874)
• Study demonstrates the ATP-sensitive interaction of the cofilin phosphatase chronophin (CIN) with the chaperone hsp90 to form a biosensor that mediates cofilin/actin rod formation. (PMID:19000834)
• Splicing of SH3BP1 and CIN gene loci produces the novel brain specific splice variant BGIN. (PMID:23223568)
• Chronophin has a role in coordinating cell leading edge dynamics by controlling active cofilin levels (PMID:26324884)
• In non-adherent glioblastoma cell lines cultured in serum-free medium, chronophin knockdown induces phenotypic changes, e.g. in colony formation and transcription, but these are highly dependent on the cellular background. CIN knockdown in the glioblastoma cell lines NCH421k and NCH644 increased active vitamin B6 levels. (PMID:29724193)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdxp	ENSDARG00000109823
mus_musculus	Pdxp	ENSMUSG00000116165
rattus_norvegicus	Pdxp	ENSRNOG00000009570
drosophila_melanogaster	CG2680	FBGN0024995
drosophila_melanogaster	CG15739	FBGN0030347
drosophila_melanogaster	CG10352	FBGN0030348
drosophila_melanogaster	CG11291	FBGN0034713
drosophila_melanogaster	CG5577	FBGN0036759
drosophila_melanogaster	CG5567	FBGN0036760
drosophila_melanogaster	CG32487	FBGN0052487
drosophila_melanogaster	CG32488	FBGN0052488
caenorhabditis_elegans		WBGENE00016664
caenorhabditis_elegans		WBGENE00016892
caenorhabditis_elegans		WBGENE00018424
caenorhabditis_elegans		WBGENE00019604

Paralogs (3): LHPP (ENSG00000107902), HDHD2 (ENSG00000167220), PGP (ENSG00000184207)

Protein

Protein identifiers

Chronophin — Q96GD0 (reviewed: Q96GD0)

Alternative names: Pyridoxal phosphate phosphatase

All UniProt accessions (3): A0A024R1I3, B1AHD3, Q96GD0

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a pyridoxal phosphate (PLP) phosphatase, which also catalyzes the dephosphorylation of pyridoxine 5’-phosphate (PNP) and pyridoxamine 5’-phosphate (PMP), with order of substrate preference PLP > PNP > PMP and therefore plays a role in vitamin B6 metabolism. Also functions as a protein serine phosphatase that specifically dephosphorylates ‘Ser-3’ in proteins of the actin-depolymerizing factor (ADF)/cofilin family like CFL1 and DSTN. Thereby, regulates cofilin-dependent actin cytoskeleton reorganization, being required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phosphothreonines in LIMK1. Does not dephosphorylate peptides containing phosphotyrosine.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol. Cytoskeleton. Cell projection. Ruffle membrane. Lamellipodium membrane. Cell membrane.

Tissue specificity. Ubiquitously expressed (at protein level). Highly expressed in all the regions of central nerve system except the spinal cord. Also expressed at high level in liver and testis. In fetus, it is weakly expressed in all organs except brain.

Activity regulation. Inhibited by NaF, Zn(2+), Ca(2+), Mn(2+) and EDTA.

Cofactor. Divalent metal ions. Mg(2+) is the most effective.

Similarity. Belongs to the HAD-like hydrolase superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96GD0-1	CIN	yes
Q6ZT62-1	Long BGIN
Q6ZT62-2	Short BGIN

RefSeq proteins (1): NP_064711* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006349	PGP_euk	Family
IPR006357	HAD-SF_hydro_IIA	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF13242, PF13344

Enzyme classification (BRENDA):

• EC 3.1.3.74 — pyridoxal phosphatase (BRENDA: 15 organisms, 49 substrates, 69 inhibitors, 29 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PYRIDOXAL 5’-PHOSPHATE	0.0013–0.45	8
PYRIDOXINE 5’-PHOSPHATE	0.0043–0.0434	5
PYRIDOXAMINE 5’-PHOSPHATE	0.034–0.64	4
4-PYRIDOXIC ACID 5’-PHOSPHATE	0.0011–0.0026	2
PYRIDOXAL-5’-PHOSPHATE	0.33–0.385	2
4-NITROPHENYLPHOSPHATE	0.68	1
N-(5’-PHOSPHO-4’-PYRIDOXYL)BENZYLAMINE	0.0635	1
N-(5’-PHOSPHO-4’-PYRIDOXYL)ETHANOLAMINE	0.0786	1
N-(5’-PHOSPHO-4’-PYRIDOXYL)GLYCINE	0.0143	1
N-(5’-PHOSPHO-4’-PYRIDOXYL)PHENYLALANINE	0.0082	1
PYRIDOXINE-5’-PHOSPHATE	0.385	1

Catalyzed reactions (Rhea), 4 shown:

• pyridoxal 5’-phosphate + H2O = pyridoxal + phosphate (RHEA:20533)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• pyridoxine 5’-phosphate + H2O = pyridoxine + phosphate (RHEA:25112)
• pyridoxamine + phosphate = pyridoxamine 5’-phosphate + H2O (RHEA:25135)

UniProt features (39 total): helix 14, strand 13, binding site 6, active site 2, turn 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8S8A	X-RAY DIFFRACTION	1.5
9EM1	X-RAY DIFFRACTION	1.5
2OYC	X-RAY DIFFRACTION	1.72
2CFT	X-RAY DIFFRACTION	1.8
2P27	X-RAY DIFFRACTION	1.9
5GYN	X-RAY DIFFRACTION	2
2P69	X-RAY DIFFRACTION	2.25
2CFR	X-RAY DIFFRACTION	2.4
2CFS	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GD0-F1	96.12	0.94

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): 25 (nucleophile); 27 (proton donor)

Ligand- & substrate-binding residues (6): 25; 27; 58–60; 182; 213; 238

Mutagenesis-validated functional residues (1):

Position	Phenotype
25	abolishes protein phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_ALDEHYDE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOCC_RUFFLE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_CELLULAR_RESPONSE_TO_ATP, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (9): protein dephosphorylation (GO:0006470), regulation of mitotic nuclear division (GO:0007088), dephosphorylation (GO:0016311), positive regulation of actin filament depolymerization (GO:0030836), actin rod assembly (GO:0031247), pyridoxal 5’-phosphate catabolic process (GO:0032361), regulation of cytokinesis (GO:0032465), cellular response to ATP (GO:0071318), regulation of modification of postsynaptic structure (GO:0099159)

GO Molecular Function (10): magnesium ion binding (GO:0000287), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), heat shock protein binding (GO:0031072), pyridoxal phosphatase activity (GO:0033883), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), metal ion binding (GO:0046872)

GO Cellular Component (16): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), cell-cell junction (GO:0005911), lamellipodium membrane (GO:0031258), ruffle membrane (GO:0032587), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), membrane (GO:0016020), lamellipodium (GO:0030027), midbody (GO:0030496), cleavage furrow (GO:0032154), cell projection (GO:0042995), contractile ring (GO:0070938)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
regulation of cell cycle process	2
phosphatase activity	2
cell projection membrane	2
leading edge membrane	2
synapse	2
dephosphorylation	1
protein modification process	1
regulation of mitotic cell cycle	1
regulation of nuclear division	1
mitotic nuclear division	1
phosphate-containing compound metabolic process	1
actin filament depolymerization	1
regulation of actin filament depolymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of protein depolymerization	1
positive regulation of supramolecular fiber organization	1
actin filament bundle assembly	1
vitamin B6 catabolic process	1
pyridoxal 5’-phosphate metabolic process	1
aldehyde catabolic process	1
organophosphate catabolic process	1
cytokinesis	1
regulation of cell division	1
response to ATP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
modification of postsynaptic structure	1
regulation of modification of synaptic structure	1
metal ion binding	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDXP	CFL2	Q9Y281	893
PDXP	CFL1	P23528	886
PDXP	LIMK1	P53667	786
PDXP	PSME3	P61289	693
PDXP	HSP90AA1	P07900	688
PDXP	HSP90AB1	P08238	685
PDXP	SSH1	Q8WYL5	679
PDXP	PDXK	O00764	670
PDXP	PNPO	Q9NVS9	647
PDXP	TESK1	Q15569	571
PDXP	SSH3	Q8TE77	555
PDXP	PPP1CA	P08129	553
PDXP	LIMK2	P53671	532
PDXP	SSH2	Q76I76	522
PDXP	ARRB1	P49407	516

IntAct

25 interactions, top by confidence:

A	B	Type	Score
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
NDUFAF5	XRCC2	psi-mi:“MI:0914”(association)	0.530
RDH12	NME2P1	psi-mi:“MI:0914”(association)	0.530
Arrb1	PDXP	psi-mi:“MI:0915”(physical association)	0.400
PDXP	Arrb1	psi-mi:“MI:0915”(physical association)	0.400
PDXP	STK11	psi-mi:“MI:0915”(physical association)	0.370
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
MPL	FAM171A2	psi-mi:“MI:0914”(association)	0.350
CENPM	DNM1L	psi-mi:“MI:0914”(association)	0.350
NFYA	NME2P1	psi-mi:“MI:0914”(association)	0.350
PLA2G7	TUBA3C	psi-mi:“MI:0914”(association)	0.350
SLC25A32	AKR1A1	psi-mi:“MI:0914”(association)	0.350
ZDHHC16	PCK1	psi-mi:“MI:0914”(association)	0.350
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
SMNDC1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

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

ESM2 similar proteins: A4FV98, A5PK51, A6NDG6, E1BE10, O00587, O35595, O95294, P60487, Q12788, Q17QS4, Q1JPJ0, Q2T9S4, Q2TBI8, Q32NY4, Q3T063, Q3ZBF9, Q501J2, Q5E9V4, Q5F4B1, Q5IS64, Q5SUV1, Q5T9C9, Q6AYG0, Q6AYR8, Q6XQN1, Q6XQN6, Q6ZMM2, Q80US4, Q8BNV1, Q8BZG5, Q8CC86, Q8IZ69, Q8N9H8, Q8NE01, Q8R2H9, Q8TCT1, Q8VCA8, Q8VD52, Q969S8, Q96AZ1

Diamond homologs: A6NDG6, D3ZDK7, P0AF24, P0AF25, P0DKC3, P0DKC4, P19881, P34492, P46351, P60487, P94512, Q00472, Q2FIE5, Q2FZX0, Q2T9S4, Q2YWR1, Q3ZBF9, Q5F4B1, Q5HHF6, Q6GAZ7, Q6GIF9, Q6ZT62, Q7A1D4, Q7A6K4, Q8CHP8, Q8GWU0, Q8VD52, Q96GD0, Q99VE8, O33194, A4QFW4, O26311, O32125, P0A8Y1, P0A8Y2, Q49W68, Q4L4U2, Q5HQN3, Q8CPW3, P94526

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PDXP	“down-regulates activity”	MDM2	dephosphorylation
PDXP	“down-regulates activity”	CFL1	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

214 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37665549:CTACA:C	acceptor_loss	1.0000
22:37665550:TACA:T	acceptor_loss	1.0000
22:37665551:ACAGG:A	acceptor_loss	1.0000
22:37665552:CAGG:C	acceptor_loss	1.0000
22:37665554:G:C	acceptor_loss	1.0000
22:37659353:CCTGG:C	donor_loss	0.9900
22:37659354:CTGG:C	donor_loss	0.9900
22:37659355:TGG:T	donor_loss	0.9900
22:37659356:GGT:G	donor_loss	0.9900
22:37659357:G:T	donor_loss	0.9900
22:37659358:TGAG:T	donor_loss	0.9900
22:37659359:GA:G	donor_loss	0.9900
22:37665553:A:AG	acceptor_gain	0.9900
22:37665553:AG:A	acceptor_gain	0.9900
22:37665554:G:GT	acceptor_gain	0.9900
22:37665554:GG:G	acceptor_gain	0.9900
22:37665554:GGC:G	acceptor_gain	0.9900
22:37665554:GGCA:G	acceptor_gain	0.9900
22:37665554:GGCAC:G	acceptor_gain	0.9900
22:37659357:G:GG	donor_gain	0.9700
22:37665551:A:AG	acceptor_gain	0.9700
22:37665551:ACAG:A	acceptor_gain	0.9600
22:37664025:GGCT:G	donor_gain	0.9400
22:37665552:C:G	acceptor_gain	0.9300
22:37659361:G:C	donor_loss	0.9200
22:37659421:GG:G	donor_gain	0.8900
22:37659422:GG:G	donor_gain	0.8900
22:37664026:GCT:G	donor_gain	0.8900
22:37659332:C:G	donor_gain	0.8800
22:37659360:AGCG:A	donor_loss	0.8700

AlphaMissense

1879 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37665708:A:C	D243A	0.999
22:37665708:A:T	D243V	0.999
22:37658958:A:T	N59I	0.998
22:37658959:C:A	N59K	0.998
22:37658959:C:G	N59K	0.998
22:37665693:A:C	D238A	0.998
22:37665693:A:T	D238V	0.998
22:37665707:G:C	D243H	0.998
22:37665708:A:G	D243G	0.998
22:37665709:C:A	D243E	0.998
22:37665709:C:G	D243E	0.998
22:37665619:G:C	K213N	0.997
22:37665619:G:T	K213N	0.997
22:37665693:A:G	D238G	0.997
22:37665707:G:T	D243Y	0.997
22:37658856:A:T	D25V	0.996
22:37658857:C:A	D25E	0.996
22:37658857:C:G	D25E	0.996
22:37665563:A:C	S195R	0.996
22:37665565:C:A	S195R	0.996
22:37665565:C:G	S195R	0.996
22:37665617:A:C	K213Q	0.996
22:37665618:A:C	K213T	0.996
22:37665690:G:T	G237V	0.996
22:37665694:C:A	D238E	0.996
22:37665694:C:G	D238E	0.996
22:37665720:G:A	G247D	0.996
22:37665720:G:T	G247V	0.996
22:37665819:C:A	P280H	0.996
22:37658862:A:T	D27V	0.995

dbSNP variants (sampled 300 via entrez): RS1000156018 (22:37658458 C>T), RS1000231707 (22:37657886 C>T), RS1000286638 (22:37664089 C>T), RS1000679352 (22:37663789 T>G), RS1001377767 (22:37666429 G>A), RS1002042308 (22:37658468 A>G,T), RS1002072374 (22:37658165 G>A,C), RS1002085844 (22:37664473 G>A,T), RS1002344931 (22:37662617 G>T), RS1002641866 (22:37660013 T>C), RS1002799906 (22:37665455 G>A,C,T), RS1003477662 (22:37659753 T>C), RS1004048637 (22:37661293 C>T), RS1004190892 (22:37660108 T>C), RS1004293423 (22:37666074 C>G,T)

Disease associations

OMIM: gene MIM:609246 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001343_4	Fat distribution (HIV)	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression	2
aristolochic acid I	increases expression	1
afuresertib	decreases expression	1
lead acetate	decreases expression	1
sodium arsenate	increases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, increases expression	1
vanadyl sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Estradiol	increases expression	1
Fluorouracil	decreases expression	1
Formaldehyde	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Oxygen	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
Thapsigargin	decreases expression	1

Clinical trials (associated diseases)

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