PHLDA2

Summary

PHLDA2 (pleckstrin homology like domain family A member 2, HGNC:12385) is a protein-coding gene on chromosome 11p15.4, encoding Pleckstrin homology-like domain family A member 2 (Q53GA4). Plays a role in regulating placenta growth.

This gene is located in a cluster of imprinted genes on chromosome 11p15.5, which is considered to be an important tumor suppressor gene region. Alterations in this region may be associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene has been shown to be imprinted, with preferential expression from the maternal allele in placenta and liver.

Source: NCBI Gene 7262 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 34 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12385
Approved symbol	PHLDA2
Name	pleckstrin homology like domain family A member 2
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	IPL, BWR1C, HLDA2
Ensembl gene	ENSG00000181649
Ensembl biotype	protein_coding
OMIM	602131
Entrez	7262

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000314222, ENST00000718435

RefSeq mRNA: 1 — MANE Select: NM_003311 NM_003311

CCDS: CCDS7741

Canonical transcript exons

ENST00000314222 — 2 exons

Exon	Start	End
ENSE00001213822	2928273	2928667
ENSE00003818555	2928896	2929420

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 98.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.3837 / max 1821.5434, expressed in 1702 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118250	104.2925	1702
118251	0.0912	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	98.07	gold quality
mucosa of transverse colon	UBERON:0004991	92.35	gold quality
lower esophagus mucosa	UBERON:0035834	89.05	gold quality
esophagus mucosa	UBERON:0002469	88.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.89	gold quality
stromal cell of endometrium	CL:0002255	83.72	gold quality
skin of abdomen	UBERON:0001416	83.04	gold quality
vagina	UBERON:0000996	82.46	gold quality
ascending aorta	UBERON:0001496	81.19	gold quality
thoracic aorta	UBERON:0001515	81.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.43	gold quality
prostate gland	UBERON:0002367	80.40	gold quality
zone of skin	UBERON:0000014	80.12	gold quality
transverse colon	UBERON:0001157	79.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.67	silver quality
right coronary artery	UBERON:0001625	79.48	gold quality
left coronary artery	UBERON:0001626	78.94	gold quality
skin of leg	UBERON:0001511	78.59	gold quality
descending thoracic aorta	UBERON:0002345	78.20	gold quality
ectocervix	UBERON:0012249	78.12	gold quality
body of stomach	UBERON:0001161	78.00	gold quality
esophagus	UBERON:0001043	77.81	gold quality
omental fat pad	UBERON:0010414	77.63	gold quality
left uterine tube	UBERON:0001303	76.50	gold quality
metanephros cortex	UBERON:0010533	76.38	gold quality
duodenum	UBERON:0002114	76.07	gold quality
minor salivary gland	UBERON:0001830	75.62	gold quality
upper lobe of left lung	UBERON:0008952	74.94	gold quality
saliva-secreting gland	UBERON:0001044	74.82	gold quality
adipose tissue	UBERON:0001013	74.31	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	4287.79
E-MTAB-6701	yes	3619.29
E-HCAD-23	yes	749.09
E-HCAD-1	yes	559.84
E-ENAD-20	yes	170.87
E-CURD-114	yes	63.02
E-MTAB-8410	yes	24.28
E-GEOD-125970	yes	20.21
E-MTAB-6678	yes	17.11
E-HCAD-10	yes	16.48
E-MTAB-9689	no	209.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting PHLDA2, 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-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-376C-3P	97.63	68.88	1263
HSA-MIR-379-5P	97.52	67.81	485
HSA-MIR-3529-5P	97.12	67.06	440
HSA-MIR-4515	95.70	65.73	716

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 34)

• Transcripts of TSSC3 could not be detected in human oocytes and preimplantation embryos. (PMID:15952111)
• Exposure of trophoblasts to hypoxia in vitro markedly reduced the expression of PHLDA2. (PMID:16584773)
• association with low birth weight (PMID:17180344)
• Up-regulation of TSSC3 occurred in Dicer knockdown cells. (PMID:17303335)
• Expression levels of PHLDA2 gene were upregulated in the first trimester pregnancy (PMID:20484977)
• PHLDA2 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• TSSC3 has a potent tumor suppressor role in osteosarcoma, probably by inhibition of growth and induction of apoptosis via the mitochondrial apoptosis pathway. (PMID:22021909)
• The results suggest that placental PHLDA2 may provide a biomarker for suboptimal skeletal growth in pregnancies uncomplicated by overt fetal growth restriction. (PMID:22100507)
• A luciferase reporter assay was used to identify in the PHLDA2 promoter a 15 bp repeat sequence variant that significantly reduces PHLDA2-promoter efficiency. Maternal inheritance of the variant resulted in a significant increase in birth weight. (PMID:22444668)
• TSSC3 inhibits osteosarcoma tumorigenicity through reducing stemness and promoting apoptosis of tumor inducing cells (PMID:22610481)
• TSSC3 overexpression suppressed osteosarcoma cell growth and increased apoptosis through caspase-3 upregulation, suggesting that TSSC3 may play a pro-apoptosis role to maintain the normal balance of growth (PMID:24268429)
• results suggest upregulated pleckstrin homology-like domain family A member 2 (PHLDA2) in placenta of monozygotic twins may be associated with the pathogenesis of singleton intrauterine growth restriction (PMID:24703004)
• elevated expression in placenta of growth restricted pregnancies [review] (PMID:24953163)
• The gene expression pattern of CDKN1C, H19, IGF2, KCNQ1 and PHLDA2 genes was evaluated using RT-PCR. (PMID:24986528)
• PHLDA2 may promote the occurrence/development of preeclampsia by inhibiting proliferation/migration/invasion of trophoblasts. (PMID:26218012)
• TSSC3 downregulation promotes the Epithelial to mesenchymal transition (EMT) of osteosarcoma cells by regulating EMT markers via a signal transduction pathway that involves Snail, Wnt-beta-catenin/TCF, and GSK-3beta (PMID:26845447)
• PHLDA2 plays an important role in the occurrence and development of pregnancy complications by promoting trophoblast apoptosis and suppressing cell invasion. (PMID:26935516)
• Placental PHLDA2 expression was significantly 2.3 fold higher in reduced fetal movements pregnancies resulting in delivery of a growth restricted compared with a normal birth weight infant. (PMID:26944942)
• TSSC3 was a prognostic marker in osteosarcoma. (PMID:27044808)
• RanBP9/TSSC3 complex cooperatively suppress metastasis via downregulation of Src-dependent Akt pathway to expedite mitochondrial-associated anoikis. (PMID:28032865)
• Authors demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. (PMID:30092789)
• Increased CDKN1C and PHLDA2 and reduced IGF-2 abundances in placental tissue were related to BW and early period catch-up growth in full-term SGA infants. (PMID:31194812)
• PHLDA2 gene polymorphisms and risk of HELLP syndrome and severe preeclampsia. (PMID:32062476)
• PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway. (PMID:32385195)
• Prognostic and predictive value of Pleckstrin homology-like domain, family A family members in breast cancer. (PMID:33179538)
• PHLDA3 promotes lung adenocarcinoma cell proliferation and invasion via activation of the Wnt signaling pathway. (PMID:34006890)
• Tumor-Suppressing STF cDNA 3 Overexpression Suppresses Renal Fibrosis by Alleviating Anoikis Resistance and Inhibiting the PI3K/Akt Pathway. (PMID:34284400)
• HGF-mediated Up-regulation of PHLDA2 Is Associated With Apoptosis in Gastric Cancer. (PMID:34475057)
• RhoGDI1 interacts with PHLDA2, suppresses the proliferation, migration, and invasion of trophoblast cells, and participates in the pathogenesis of preeclampsia. (PMID:35841528)
• Knockdown of PHLDA2 promotes apoptosis and autophagy of glioma cells through the AKT/mTOR pathway. (PMID:35894264)
• FOSL1 transcriptionally regulates PHLDA2 to promote 5-FU resistance in colon cancer cells. (PMID:37178619)
• Diagnostic Utility of TSSC3 and RB1 Immunohistochemistry in Hydatidiform Mole. (PMID:37298606)
• PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma. (PMID:38827322)
• PHLDA2 gene is imprinted, with preferential expression from the maternal allele in placenta and liver. (PMID:9328465)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	phlda2	ENSDARG00000042874
mus_musculus	Phlda2	ENSMUSG00000010760
rattus_norvegicus	Phlda2	ENSRNOG00000020614

Paralogs (2): PHLDA1 (ENSG00000139289), PHLDA3 (ENSG00000174307)

Protein

Protein identifiers

Pleckstrin homology-like domain family A member 2 — Q53GA4 (reviewed: Q53GA4)

Alternative names: Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene C protein, Imprinted in placenta and liver protein, Tumor-suppressing STF cDNA 3 protein, Tumor-suppressing subchromosomal transferable fragment candidate gene 3 protein, p17-Beckwith-Wiedemann region 1 C

All UniProt accessions (1): Q53GA4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in regulating placenta growth. May act via its PH domain that competes with other PH domain-containing proteins, thereby preventing their binding to membrane lipids.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Expressed in placenta and adult prostate gland. In placenta, it is present in all cells of the villous cytotrophoblast. The protein is absent in cells from hydatidiform moles. Hydatidiform mole is a gestation characterized by abnormal development of both fetus and trophoblast. The majority of hydatidiform moles are associated with an excess of paternal to maternal genomes and are likely to result from the abnormal expression of imprinted genes (at protein level). Expressed at low levels in adult liver and lung, and fetal liver. Expressed in adult brain and neuroblastoma, medullablastoma and glioblastoma cell lines.

Domain organisation. The PH domain binds phosphoinositides with a broad specificity. It may compete with the PH domain of some other proteins, thereby interfering with their binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3).

Induction. Maternal PHLDA2 allele is activated, while paternal Phlda2 is repressed due to genomic imprinting. Down-regulated by hypoxia. Although highly similar to PHLDA3 protein, it is not regulated by p53/TP53.

Miscellaneous. The PHLDA2 locus is imprinted. Loss of imprinting results in overexpression. Imprinting is dependent on RNAi machinery.

Similarity. Belongs to the PHLDA2 family.

RefSeq proteins (1): NP_003302* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR042832	PHLA1/2/3	Family

UniProt features (11 total): modified residue 5, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53GA4-F1	86.07	0.62

Functional residue map

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

Post-translational modifications (5): 3, 42, 141, 144, 151

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 251 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, MODULE_52, SHEPARD_BMYB_MORPHOLINO_UP, AP1_01, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SWEET_KRAS_ONCOGENIC_SIGNATURE, ENK_UV_RESPONSE_KERATINOCYTE_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, NAGASHIMA_NRG1_SIGNALING_UP, VETTER_TARGETS_OF_PRKCA_AND_ETS1_DN, SHIRAISHI_PLZF_TARGETS_UP

GO Biological Process (8): placenta development (GO:0001890), apoptotic process (GO:0006915), animal organ morphogenesis (GO:0009887), regulation of gene expression (GO:0010468), regulation of cell migration (GO:0030334), positive regulation of apoptotic process (GO:0043065), regulation of embryonic development (GO:0045995), regulation of glycogen metabolic process (GO:0070873)

GO Molecular Function (2): phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
anatomical structure morphogenesis	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cell migration	1
regulation of cell motility	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
embryo development	1
regulation of multicellular organismal development	1
glycogen metabolic process	1
regulation of polysaccharide metabolic process	1
regulation of generation of precursor metabolites and energy	1
phospholipid binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHLDA2	SLC67A1	Q96BI1	952
PHLDA2	CDKN1C	P49918	928
PHLDA2	KCNQ1	P51787	904
PHLDA2	ASCL2	Q99929	902
PHLDA2	TSSC4	Q9Y5U2	883
PHLDA2	IGF2	P01344	851
PHLDA2	SLC67A1-AS	Q8N1D0	820
PHLDA2	NAP1L4	Q99733	813
PHLDA2	TSPAN32	Q96QS1	739
PHLDA2	OSBPL5	Q9H0X9	723
PHLDA2	DYNC1I2	Q13409	700
PHLDA2	SNRPN	P14648	679
PHLDA2	IGF2R	P11717	670
PHLDA2	CD81	P18582	640
PHLDA2	MEST	Q5EB52	633

IntAct

21 interactions, top by confidence:

A	B	Type	Score
PHLDA2	SSX2	psi-mi:“MI:0915”(physical association)	0.560
FCHO1	PHLDA2	psi-mi:“MI:0915”(physical association)	0.560
PHLDA2	OTUB2	psi-mi:“MI:0915”(physical association)	0.560
SSX2	PHLDA2	psi-mi:“MI:0915”(physical association)	0.560
Cenpe	BBX	psi-mi:“MI:0914”(association)	0.350
Kctd5		psi-mi:“MI:0914”(association)	0.350
SUCO	RPL10	psi-mi:“MI:0914”(association)	0.350
ELK1	TPP1	psi-mi:“MI:0914”(association)	0.350
ELK1	PPP6C	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
FAM170A	MCM3AP	psi-mi:“MI:0914”(association)	0.350
PHLDA2	FCHO1	psi-mi:“MI:0915”(physical association)	0.000
PHLDA2	OTUB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): PHLDA2 (Affinity Capture-MS), PHLDA2 (Affinity Capture-MS), PHLDA2 (Affinity Capture-MS), RANBP9 (Two-hybrid), RANBP9 (Affinity Capture-Western), PHLDA2 (Affinity Capture-Western), PHLDA2 (Affinity Capture-Western), SRC (Affinity Capture-Western), PHLDA2 (Two-hybrid), PHLDA2 (Two-hybrid), SSX2 (Two-hybrid), SSX2B (Two-hybrid), PHLDA2 (Affinity Capture-MS), PHLDA2 (Affinity Capture-MS), PHLDA2 (Affinity Capture-MS)

ESM2 similar proteins: A1L2W9, B2RQE8, B5XG43, G9CGD6, O08969, O88387, P59113, Q0V987, Q0VC85, Q1KKW7, Q1KKZ1, Q32LP0, Q3UUV5, Q3ZBA3, Q4V7G1, Q503L1, Q53GA4, Q5FVW6, Q5PQT7, Q5R8M5, Q5U597, Q5XGP7, Q5ZL23, Q6P0G8, Q6PG29, Q7Z628, Q7Z6J4, Q80VL0, Q80YS6, Q86UX7, Q86WV1, Q8AW35, Q8BY35, Q8IZC4, Q8K1B8, Q8N556, Q8VH46, Q91ZM9, Q91ZT5, Q925E0

Diamond homologs: A1L2W9, B5XG43, O08969, Q0V987, Q0VC85, Q503L1, Q53GA4, Q5PQT7, Q62392, Q8AW35, Q8WV24, Q9QZA1, Q9WV95, Q9Y5J5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

77 predictions. Top by Δscore:

Variant	Effect	Δscore
11:2928895:CCG:C	donor_gain	1.0000
11:2928664:GGCCC:G	acceptor_loss	0.9900
11:2928665:GCCC:G	acceptor_loss	0.9900
11:2928666:CCCTG:C	acceptor_loss	0.9900
11:2928667:CCTG:C	acceptor_loss	0.9900
11:2928668:C:CC	acceptor_gain	0.9900
11:2928669:T:G	acceptor_loss	0.9900
11:2928889:CACT:C	donor_loss	0.9900
11:2928890:ACTC:A	donor_loss	0.9900
11:2928892:TCAC:T	donor_loss	0.9900
11:2928893:CACCG:C	donor_loss	0.9900
11:2928894:A:AC	donor_gain	0.9900
11:2928894:A:AT	donor_loss	0.9900
11:2928895:C:CC	donor_gain	0.9900
11:2928895:C:CT	donor_loss	0.9900
11:2928895:CCGCG:C	donor_gain	0.9900
11:2928663:TGGCC:T	acceptor_gain	0.9800
11:2928665:GCC:G	acceptor_gain	0.9800
11:2928666:CC:C	acceptor_gain	0.9800
11:2928666:CCC:C	acceptor_gain	0.9800
11:2928667:CC:C	acceptor_gain	0.9800
11:2928894:ACCG:A	donor_gain	0.9800
11:2928895:CCGC:C	donor_gain	0.9800
11:2928664:GGCC:G	acceptor_gain	0.9700
11:2928894:AC:A	donor_gain	0.9700
11:2928895:CC:C	donor_gain	0.9700
11:2929021:T:A	donor_gain	0.9500
11:2928888:TCAC:T	donor_loss	0.9000
11:2928668:C:T	acceptor_gain	0.8600
11:2928890:A:AC	donor_gain	0.8600

AlphaMissense

988 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:2929119:G:C	F82L	1.000
11:2929119:G:T	F82L	1.000
11:2929120:A:G	F82S	1.000
11:2929121:A:G	F82L	1.000
11:2929155:G:C	F70L	1.000
11:2929155:G:T	F70L	1.000
11:2929157:A:G	F70L	1.000
11:2929293:C:A	W24C	1.000
11:2929293:C:G	W24C	1.000
11:2929295:A:G	W24R	1.000
11:2929295:A:T	W24R	1.000
11:2929084:A:T	I94N	0.999
11:2929095:C:A	W90C	0.999
11:2929095:C:G	W90C	0.999
11:2929097:A:G	W90R	0.999
11:2929097:A:T	W90R	0.999
11:2929120:A:C	F82C	0.999
11:2929122:G:C	D81E	0.999
11:2929122:G:T	D81E	0.999
11:2929150:A:T	I72N	0.999
11:2929153:G:A	T71I	0.999
11:2929156:A:G	F70S	0.999
11:2929273:A:T	L31H	0.999
11:2929294:C:G	W24S	0.999
11:2929319:G:T	R16S	0.999
11:2929320:C:A	K15N	0.999
11:2929320:C:G	K15N	0.999
11:2929327:A:G	L13S	0.999
11:2929118:G:T	R83S	0.998
11:2929123:T:A	D81V	0.998

dbSNP variants (sampled 300 via entrez): RS1000148322 (11:2929605 C>T), RS1000633419 (11:2929784 G>A,C), RS1000962965 (11:2929951 T>C), RS1001765868 (11:2929045 A>C,G), RS1002235960 (11:2931282 C>T), RS1003037422 (11:2927850 G>A), RS1006380064 (11:2930206 T>C), RS1006894635 (11:2930786 G>A), RS1007183657 (11:2929654 G>A), RS1007292535 (11:2931065 G>A), RS1008376799 (11:2930322 A>G), RS1008786951 (11:2931375 G>A), RS1008847673 (11:2928717 C>T), RS1008869086 (11:2928529 A>C,G), RS1009270770 (11:2929966 A>G)

Disease associations

OMIM: gene MIM:602131 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000769_7	Calcium levels	5.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	8
Benzo(a)pyrene	increases expression, increases methylation	7
Aflatoxin B1	affects expression, increases expression	5
methylmercuric chloride	affects cotreatment, increases expression	4
Estradiol	decreases expression, increases expression, affects expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases expression, affects expression	3
Cyclosporine	increases expression	3
bisphenol A	affects expression, affects cotreatment, decreases expression	2
cobaltous chloride	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Cisplatin	decreases expression, increases response to substance, affects reaction	2
Hydrogen Peroxide	affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cadmium Chloride	increases expression	2
Genistein	increases expression	2
tert-Butylhydroperoxide	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Vitamin K 3	affects expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1

Clinical trials (associated diseases)

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