BPNT2

Summary

BPNT2 (3’(2’), 5’-bisphosphate nucleotidase 2, HGNC:26019) is a protein-coding gene on chromosome 8q12.1, encoding Golgi-resident adenosine 3’,5’-bisphosphate 3’-phosphatase (Q9NX62). Exhibits 3’-nucleotidase activity toward adenosine 3’,5’-bisphosphate (PAP), namely hydrolyzes adenosine 3’,5’-bisphosphate into adenosine 5’-monophosphate (AMP) and a phosphate.

This gene encodes a member of the inositol monophosphatase family. The encoded protein is localized to the Golgi apparatus and catalyzes the hydrolysis of phosphoadenosine phosphate (PAP) to adenosine monophosphate (AMP). Mutations in this gene are a cause of GRAPP type chondrodysplasia with joint dislocations, and a pseudogene of this gene is located on the long arm of chromosome 1.

Source: NCBI Gene 54928 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chondrodysplasia with joint dislocations, gPAPP type (Definitive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 315 total — 11 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 31
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_017813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26019
Approved symbol	BPNT2
Name	3’(2’), 5’-bisphosphate nucleotidase 2
Location	8q12.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20421, IMPA3, gPAPP
Ensembl gene	ENSG00000104331
Ensembl biotype	protein_coding
OMIM	614010
Entrez	54928

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000262644, ENST00000517461, ENST00000520392, ENST00000972212, ENST00000972213, ENST00000972214

RefSeq mRNA: 1 — MANE Select: NM_017813 NM_017813

CCDS: CCDS6169

Canonical transcript exons

ENST00000262644 — 5 exons

Exon	Start	End
ENSE00000694642	56978050	56978145
ENSE00001122702	56980035	56980197
ENSE00001252408	56957931	56964064
ENSE00001252414	56993199	56993867
ENSE00003557793	56966191	56966352

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.2056 / max 354.5567, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93186	47.8288	1823
93185	0.3768	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	97.28	gold quality
globus pallidus	UBERON:0001875	96.90	gold quality
adrenal tissue	UBERON:0018303	96.70	gold quality
heart right ventricle	UBERON:0002080	96.13	gold quality
subthalamic nucleus	UBERON:0001906	95.64	gold quality
vena cava	UBERON:0004087	95.38	gold quality
pons	UBERON:0000988	95.34	gold quality
saphenous vein	UBERON:0007318	95.27	gold quality
lateral globus pallidus	UBERON:0002476	95.17	gold quality
middle temporal gyrus	UBERON:0002771	95.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.07	gold quality
parotid gland	UBERON:0001831	94.89	gold quality
substantia nigra pars compacta	UBERON:0001965	94.84	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.84	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.83	gold quality
superior vestibular nucleus	UBERON:0007227	94.64	gold quality
islet of Langerhans	UBERON:0000006	94.48	gold quality
biceps brachii	UBERON:0001507	94.43	gold quality
superficial temporal artery	UBERON:0001614	94.40	gold quality
tibia	UBERON:0000979	94.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.20	gold quality
stromal cell of endometrium	CL:0002255	94.14	gold quality
inferior vagus X ganglion	UBERON:0005363	93.90	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.84	gold quality
cauda epididymis	UBERON:0004360	93.78	gold quality
postcentral gyrus	UBERON:0002581	93.46	gold quality
seminal vesicle	UBERON:0000998	93.38	gold quality
parietal lobe	UBERON:0001872	93.24	gold quality
entorhinal cortex	UBERON:0002728	92.88	gold quality
mammary duct	UBERON:0001765	92.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

309 targeting BPNT2, 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-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6740-5P	100.00	65.64	932
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 4)

• Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, a Golgi-resident nucleotide phosphatase that hydrolyzes phosphoadenosine phosphate (PAP), the byproduct of sulfotransferase reactions, to AMP. (PMID:21549340)
• concluded that IMPAD1 should be screened for patients with Catel-Manzke and additional features (PMID:22887726)
• IMPAD1 functions as mitochondrial electron transport inhibitor that prevents ROS production and promotes lung cancer metastasis through the AMPK-Notch1-HEY1 pathway. (PMID:32417395)
• LncRNA BC promotes lung adenocarcinoma progression by modulating IMPAD1 alternative splicing. (PMID:36650118)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpnt2	ENSMUSG00000066324
rattus_norvegicus	Bpnt2	ENSRNOG00000046647
drosophila_melanogaster	CG17026	FBGN0036550
drosophila_melanogaster	CG17029	FBGN0036551
drosophila_melanogaster	CG17028	FBGN0036552
drosophila_melanogaster	CG17027	FBGN0036553

Paralogs (4): IMPA1 (ENSG00000133731), IMPA2 (ENSG00000141401), INPP1 (ENSG00000151689), BPNT1 (ENSG00000162813)

Protein

Protein identifiers

Golgi-resident adenosine 3’,5’-bisphosphate 3’-phosphatase — Q9NX62 (reviewed: Q9NX62)

Alternative names: 3’(2’), 5’-bisphosphate nucleotidase 2, Inositol monophosphatase domain-containing protein 1, Myo-inositol monophosphatase A3, Phosphoadenosine phosphate 3’-nucleotidase

All UniProt accessions (3): Q9NX62, H0YB38, H0YBS3

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits 3’-nucleotidase activity toward adenosine 3’,5’-bisphosphate (PAP), namely hydrolyzes adenosine 3’,5’-bisphosphate into adenosine 5’-monophosphate (AMP) and a phosphate. May play a role in the formation of skeletal elements derived through endochondral ossification, possibly by clearing adenosine 3’,5’-bisphosphate produced by Golgi sulfotransferases during glycosaminoglycan sulfation. Has no activity toward 3’-phosphoadenosine 5’-phosphosulfate (PAPS) or inositol phosphate (IP) substrates including I(1)P, I(1,4)P2, I(1,3,4)P3, I(1,4,5)P3 and I(1,3,4,5)P4.

Subcellular location. Golgi apparatus. trans-Golgi network membrane.

Post-translational modifications. Contains N-linked glycan resistant to endoglycosydase H.

Disease relevance. Chondrodysplasia with joint dislocations, GPAPP type (CDP-GPAPP) [MIM:614078] A condition consisting of congenital joint dislocations, chondrodysplasia with short stature, micrognathia and cleft palate, and a distinctive face. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Strongly inhibited by lithium.

Pathway. Sulfur metabolism.

Similarity. Belongs to the inositol monophosphatase superfamily.

RefSeq proteins (1): NP_060283* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000760	Inositol_monophosphatase-like	Family
IPR020550	Inositol_monophosphatase_CS	Conserved_site
IPR050725	CysQ/Inositol_MonoPase	Family

Pfam: PF00459

Catalyzed reactions (Rhea), 1 shown:

• adenosine 3’,5’-bisphosphate + H2O = AMP + phosphate (RHEA:10040)

UniProt features (25 total): binding site 11, sequence conflict 3, topological domain 2, sequence variant 2, active site 2, chain 1, modified residue 1, glycosylation site 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NX62-F1	88.55	0.70

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): 110 (proton acceptor); 179 (proton acceptor)

Ligand- & substrate-binding residues (11): 174; 176; 177; 242; 245; 268; 272; 300; 133; 133; 174

Post-translational modifications (1): 1

Glycosylation sites (1): 259

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations

MSigDB gene sets: 344 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_CHONDROCYTE_DEVELOPMENT, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_REPLACEMENT_OSSIFICATION, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (7): skeletal system development (GO:0001501), endochondral ossification (GO:0001958), chondrocyte development (GO:0002063), post-embryonic development (GO:0009791), embryonic digit morphogenesis (GO:0042733), phosphatidylinositol phosphate biosynthetic process (GO:0046854), chondroitin sulfate proteoglycan metabolic process (GO:0050654)

GO Molecular Function (5): 3’-nucleotidase activity (GO:0008254), 3’(2’),5’-bisphosphate nucleotidase activity (GO:0008441), metal ion binding (GO:0046872), 3’,5’-nucleotide bisphosphate phosphatase activity (GO:0097657), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), Golgi lumen (GO:0005796), cytosol (GO:0005829), endomembrane system (GO:0012505), membrane (GO:0016020), nuclear body (GO:0016604), trans-Golgi network membrane (GO:0032588), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
nucleotidase activity	2
cytoplasm	2
system development	1
replacement ossification	1
endochondral bone morphogenesis	1
chondrocyte differentiation	1
cell development	1
multicellular organism development	1
multicellular organismal process	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
glycerophospholipid biosynthetic process	1
proteoglycan metabolic process	1
cation binding	1
phosphatase activity	1
catalytic activity	1
nuclear lumen	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus	1
intracellular organelle lumen	1
vacuole	1
plasma membrane	1
nucleoplasm	1
intracellular membraneless organelle	1
trans-Golgi network	1
organelle membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1201 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPNT2	CANT1	Q8WVQ1	591
BPNT2	XKR4	Q5GH76	546
BPNT2	CHCHD7	Q9BUK0	546
BPNT2	PAPSS2	O95340	539
BPNT2	IMPA1	P29218	537
BPNT2	PAPSS1	O43252	528
BPNT2	IMPA2	O14732	501
BPNT2	FAM110B	Q8TC76	495
BPNT2	HS2ST1	Q7LGA3	493
BPNT2	PLAG1	Q6DJT9	490
BPNT2	K7EP71	K7EP71	462
BPNT2	XYLT1	Q86Y38	453
BPNT2	SLC26A2	P50443	442
BPNT2	SUMF1	Q8NBK3	426
BPNT2	TMEM68	Q96MH6	425

IntAct

43 interactions, top by confidence:

A	B	Type	Score
HLA-DRA	HLA-DRB1	psi-mi:“MI:0914”(association)	0.880
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
TNFSF13B	IPO8	psi-mi:“MI:0914”(association)	0.640
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
UST	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
MLH3	BPNT2	psi-mi:“MI:0915”(physical association)	0.400
N4BP3	BPNT2	psi-mi:“MI:0915”(physical association)	0.400
BPNT2	OCRL	psi-mi:“MI:0915”(physical association)	0.400
BPNT2		psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
HTR3C	TMEM223	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350
PCDHB11	CBX4	psi-mi:“MI:0914”(association)	0.350
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
ATP1B3	NRP2	psi-mi:“MI:0914”(association)	0.350
HLA-DRB1	CTDNEP1	psi-mi:“MI:0914”(association)	0.350
PLTP	CANX	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
EFNA5	NBAS	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
HTR3C	GET1	psi-mi:“MI:0914”(association)	0.350
PCDHGA7	SDCBP	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS)

ESM2 similar proteins: A2XEX2, D4AD37, F1RT67, F6Y5S8, O00757, O20252, O49623, O64422, P00636, P00637, P09195, P09199, P09467, P14766, P19112, P21327, P22418, P25851, P32179, P46275, P46276, P46283, P49441, P49442, P70695, Q05079, Q07204, Q14703, Q28CL4, Q29JH0, Q2KJ53, Q2KJJ9, Q2YDR3, Q38945, Q3SZB7, Q42796, Q43139, Q6NTW5, Q80V26, Q84VY5

Diamond homologs: D4AD37, F1RT67, F6Y5S8, P10497, Q28CL4, Q29JH0, Q2KJ53, Q2YDR3, Q6NTW5, Q80V26, Q869K3, Q9NX62, Q9VYF2, O95861, Q3ZCK3, Q9Z0S1, P0CY20, P0CY21, P22255, P26264, P32179, P57624, P59735, P70714, P95189, Q59XQ1, Q5BCG1, Q84VY5, Q8FAG5, Q8XCG6, Q8Z153, P21327, Q9Z1N4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	4
Uncertain significance	192
Likely benign	67
Benign	30

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1162256	NM_017813.5(BPNT2):c.473_474dup (p.Thr159Ter)	Pathogenic
151958	GRCh38/hg38 8q12.1-12.2(chr8:54821357-61146302)x1	Pathogenic
162436	NM_017813.5(BPNT2):c.324del (p.Ser108fs)	Pathogenic
2182089	NM_017813.5(BPNT2):c.118_130dup (p.Glu44fs)	Pathogenic
2426358	NC_000008.10:g.(?57876352)(57906144_?)del	Pathogenic
2713994	NM_017813.5(BPNT2):c.421C>T (p.Gln141Ter)	Pathogenic
31090	NM_017813.5(BPNT2):c.529G>A (p.Asp177Asn)	Pathogenic
31091	NM_017813.5(BPNT2):c.547A>C (p.Thr183Pro)	Pathogenic
31092	NM_017813.5(BPNT2):c.559C>T (p.Arg187Ter)	Pathogenic
4714098	NM_017813.5(BPNT2):c.532dup (p.Ala178fs)	Pathogenic
60362	GRCh38/hg38 8q12.1(chr8:55423413-58836753)x1	Pathogenic
2685311	GRCh37/hg19 8q12.1(chr8:57048524-58117681)x1	Likely pathogenic
3064488	NM_017813.5(BPNT2):c.713_714insCTTCCTATGG (p.Arg238fs)	Likely pathogenic
3068283	NM_017813.5(BPNT2):c.1007T>C (p.Leu336Pro)	Likely pathogenic
503845	NM_017813.5(BPNT2):c.972_973del (p.Ser324fs)	Likely pathogenic

SpliceAI

1031 predictions. Top by Δscore:

Variant	Effect	Δscore
8:56966185:ACAT:A	donor_loss	1.0000
8:56966186:CATAC:C	donor_loss	1.0000
8:56966187:ATAC:A	donor_loss	1.0000
8:56966188:TA:T	donor_loss	1.0000
8:56966189:A:AC	donor_gain	1.0000
8:56966189:A:AT	donor_loss	1.0000
8:56966190:C:CC	donor_gain	1.0000
8:56966196:C:CT	donor_gain	1.0000
8:56966197:C:CT	donor_gain	1.0000
8:56966258:C:A	donor_gain	1.0000
8:56966348:CCAAG:C	acceptor_gain	1.0000
8:56966349:CAAG:C	acceptor_gain	1.0000
8:56966349:CAAGC:C	acceptor_gain	1.0000
8:56966350:AAG:A	acceptor_gain	1.0000
8:56966351:AGCTG:A	acceptor_loss	1.0000
8:56966352:GC:G	acceptor_loss	1.0000
8:56966353:C:CC	acceptor_gain	1.0000
8:56966353:C:G	acceptor_loss	1.0000
8:56967108:A:AC	donor_gain	1.0000
8:56967109:C:CC	donor_gain	1.0000
8:56967109:CT:C	donor_gain	1.0000
8:56967151:A:AC	donor_gain	1.0000
8:56967152:C:CC	donor_gain	1.0000
8:56978044:TCATA:T	donor_loss	1.0000
8:56978045:CATA:C	donor_loss	1.0000
8:56978046:ATAC:A	donor_loss	1.0000
8:56978047:TACC:T	donor_loss	1.0000
8:56978048:A:AG	donor_loss	1.0000
8:56978049:CC:C	donor_loss	1.0000
8:56978141:ATCCT:A	acceptor_gain	1.0000

AlphaMissense

2336 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:56963978:A:G	W299R	1.000
8:56963978:A:T	W299R	1.000
8:56963967:A:C	C302W	0.999
8:56963968:C:T	C302Y	0.999
8:56963974:T:A	D300V	0.999
8:56963974:T:G	D300A	0.999
8:56963976:C:A	W299C	0.999
8:56963976:C:G	W299C	0.999
8:56978111:A:C	C195W	0.999
8:56980071:A:G	W172R	0.999
8:56980071:A:T	W172R	0.999
8:56963973:A:C	D300E	0.998
8:56963973:A:T	D300E	0.998
8:56963974:T:C	D300G	0.998
8:56963977:C:A	W299L	0.998
8:56978112:C:T	C195Y	0.998
8:56978113:A:G	C195R	0.998
8:56980054:A:C	D177E	0.998
8:56980054:A:T	D177E	0.998
8:56980055:T:A	D177V	0.998
8:56980056:C:G	D177H	0.998
8:56980061:G:T	P175Q	0.998
8:56980064:T:C	D174G	0.998
8:56980073:A:T	V171D	0.998
8:56980079:A:T	V169D	0.998
8:56993248:G:A	S113F	0.998
8:56963969:A:G	C302R	0.997
8:56963975:C:G	D300H	0.997
8:56978079:A:T	V206D	0.997
8:56980053:C:G	A178P	0.997

dbSNP variants (sampled 300 via entrez): RS1000017677 (8:56967438 G>T), RS1000186830 (8:56994916 T>A,C), RS1000219348 (8:56994598 A>G), RS1000264647 (8:56987095 C>A,T), RS10003 (8:56963029 G>A), RS1000306409 (8:56993260 C>T), RS1000345229 (8:56959910 A>C), RS1000443358 (8:56993023 G>A,C), RS1000448067 (8:56977682 T>G), RS1000524599 (8:56969478 G>A,C), RS1000641427 (8:56975668 T>C), RS1000734158 (8:56963378 A>T), RS1000743292 (8:56969708 T>C), RS1000844586 (8:56981376 C>T), RS1000866606 (8:56988674 T>G)

Disease associations

OMIM: gene MIM:614010 | disease phenotypes: MIM:614078

GenCC curated gene-disease

Disease	Classification	Inheritance
chondrodysplasia with joint dislocations, gPAPP type	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
chondrodysplasia with joint dislocations, gPAPP type	Moderate	AR

Mondo (1): chondrodysplasia with joint dislocations, gPAPP type (MONDO:0013561)

Orphanet (1): Chondrodysplasia with joint dislocations, gPAPP type (Orphanet:280586)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000431	Wide nasal bridge
HP:0000520	Proptosis
HP:0001156	Brachydactyly
HP:0001234	Hitchhiker thumb
HP:0001241	Capitate-hamate fusion
HP:0001377	Limited elbow extension
HP:0001385	Hip dysplasia
HP:0001773	Short foot
HP:0001831	Short toe
HP:0002857	Genu valgum
HP:0002945	Intervertebral space narrowing
HP:0002999	Patellar dislocation
HP:0003026	Short long bone
HP:0003048	Radial head subluxation
HP:0003196	Short nose
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0004440	Coronal craniosynostosis
HP:0004976	Knee dislocation
HP:0005001	Recurrent patellar dislocation
HP:0009190	Irregular epiphyses of the metacarpals
HP:0009826	Limb undergrowth
HP:0010049	Short metacarpal
HP:0012368	Flat face

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002788_5	Milk allergy	7.000000e-06
GCST003809_3	Response to selective serotonin reuptake inhibitors and depression	1.000000e-06
GCST004494_3	Hand grip strength	4.000000e-06
GCST004711_17	Alcohol dependence	3.000000e-07
GCST006585_2561	Blood protein levels	2.000000e-34

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007019	milk allergy measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0006941	grip strength measurement
EFO:0007835	alcohol dependence measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
bisphenol A	increases expression, decreases expression, increases methylation, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
sodium arsenate	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Cytarabine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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