PGAP2

Summary

PGAP2 (post-GPI attachment to proteins 2, HGNC:17893) is a protein-coding gene on chromosome 11p15.4, encoding Acyltransferase PGAP2 (Q9UHJ9). Involved in the fatty acid remodeling steps of GPI-anchor maturation where the unsaturated acyl chain at sn-2 of inositol phosphate is replaced by a saturated stearoyl chain.

The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability.

Source: NCBI Gene 27315 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperphosphatasia with intellectual disability syndrome 3 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 166 total — 6 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 91
• MANE Select transcript: NM_014489

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17893
Approved symbol	PGAP2
Name	post-GPI attachment to proteins 2
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	FRAG1, CWH43-N
Ensembl gene	ENSG00000148985
Ensembl biotype	protein_coding
OMIM	615187
Entrez	27315

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 29 protein_coding, 12 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000278243, ENST00000300730, ENST00000396986, ENST00000396991, ENST00000396993, ENST00000459679, ENST00000463452, ENST00000464229, ENST00000464261, ENST00000464441, ENST00000464590, ENST00000464906, ENST00000465237, ENST00000465307, ENST00000469307, ENST00000475884, ENST00000477358, ENST00000478773, ENST00000479072, ENST00000483829, ENST00000485602, ENST00000487112, ENST00000489571, ENST00000490830, ENST00000493547, ENST00000495026, ENST00000496834, ENST00000524661, ENST00000525937, ENST00000527810, ENST00000528216, ENST00000528526, ENST00000529944, ENST00000532017, ENST00000532523, ENST00000532535, ENST00000534498, ENST00000864245, ENST00000864246, ENST00000864247, ENST00000864248, ENST00000864249, ENST00000864250, ENST00000864251, ENST00000864252, ENST00000917636, ENST00000917637, ENST00000953444

RefSeq mRNA: 20 — MANE Select: NM_014489 NM_001145438, NM_001256235, NM_001256236, NM_001256237, NM_001256238, NM_001256239, NM_001256240, NM_001283038, NM_001283039, NM_001283040, NM_001346397, NM_001346398, NM_001346399, NM_001346400, NM_001346401, NM_001346402, NM_001346403, NM_001346404, NM_001346405, NM_014489

CCDS: CCDS44523, CCDS58112, CCDS58113, CCDS73244, CCDS73245, CCDS7747, CCDS86171, CCDS86172

Canonical transcript exons

ENST00000278243 — 7 exons

Exon	Start	End
ENSE00001845951	3808560	3808651
ENSE00003496815	3824270	3824376
ENSE00003567135	3823883	3824135
ENSE00003621542	3825328	3826371
ENSE00003689594	3817353	3817535
ENSE00003733381	3811250	3811424
ENSE00003777818	3825020	3825128

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 96.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5593 / max 224.7513, expressed in 1809 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112735	10.0770	1788
112737	8.9703	1723
112738	0.2915	20
112736	0.1756	72
112739	0.0449	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	96.75	gold quality
lower esophagus mucosa	UBERON:0035834	96.08	gold quality
skin of abdomen	UBERON:0001416	95.38	gold quality
skin of leg	UBERON:0001511	95.12	gold quality
olfactory bulb	UBERON:0002264	94.43	gold quality
zone of skin	UBERON:0000014	94.19	gold quality
type B pancreatic cell	CL:0000169	93.98	gold quality
right uterine tube	UBERON:0001302	93.96	gold quality
apex of heart	UBERON:0002098	93.95	gold quality
seminal vesicle	UBERON:0000998	93.79	gold quality
esophagus mucosa	UBERON:0002469	93.11	gold quality
left testis	UBERON:0004533	93.08	gold quality
right testis	UBERON:0004534	93.08	gold quality
body of pancreas	UBERON:0001150	92.86	gold quality
right lobe of thyroid gland	UBERON:0001119	92.32	gold quality
right lobe of liver	UBERON:0001114	92.03	gold quality
tongue squamous epithelium	UBERON:0006919	91.86	gold quality
left lobe of thyroid gland	UBERON:0001120	91.62	gold quality
upper arm skin	UBERON:0004263	91.61	gold quality
cauda epididymis	UBERON:0004360	91.42	gold quality
mucosa of transverse colon	UBERON:0004991	91.41	gold quality
testis	UBERON:0000473	91.19	gold quality
oocyte	CL:0000023	91.07	gold quality
thyroid gland	UBERON:0002046	91.05	gold quality
secondary oocyte	CL:0000655	91.02	gold quality
gingival epithelium	UBERON:0001949	90.53	gold quality
right lung	UBERON:0002167	90.45	gold quality
pituitary gland	UBERON:0000007	90.33	gold quality
pancreas	UBERON:0001264	90.14	gold quality
minor salivary gland	UBERON:0001830	90.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	285.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting PGAP2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6860	97.21	66.31	1656

Literature-anchored findings (GeneRIF, showing 4)

• Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause autosomal-recessive intellectual disability. (PMID:23561846)
• PGAP2 mutations, affecting the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation syndrome. (PMID:23561847)
• A Rare Variant in PGAP2 Causes Autosomal Recessive Hyperphosphatasia with Mental Retardation Syndrome, with a Mild Phenotype in Heterozygous Carriers. (PMID:29119105)
• A post glycosylphosphatidylinositol (GPI) attachment to proteins, type 2 (PGAP2) variant identified in Mabry syndrome index cases: Molecular genetics of the prototypical inherited GPI disorder. (PMID:31805394)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgap2	ENSDARG00000044596
mus_musculus	Pgap2	ENSMUSG00000030990
rattus_norvegicus	Pgap2	ENSRNOG00000020371
rattus_norvegicus	AABR07038703.1	ENSRNOG00000051223
drosophila_melanogaster	CG7990	FBGN0030997
drosophila_melanogaster	CG15880	FBGN0031283
drosophila_melanogaster	PGAP2	FBGN0031284
caenorhabditis_elegans		WBGENE00007045
caenorhabditis_elegans		WBGENE00012433
caenorhabditis_elegans		WBGENE00012610
caenorhabditis_elegans		WBGENE00015753
caenorhabditis_elegans		WBGENE00018113
caenorhabditis_elegans		WBGENE00020720
caenorhabditis_elegans		WBGENE00044480

Protein

Protein identifiers

Acyltransferase PGAP2 — Q9UHJ9 (reviewed: Q9UHJ9)

Alternative names: FGF receptor-activating protein 1, Post-GPI attachment to proteins factor 2

All UniProt accessions (14): Q9UHJ9, A0A024RCD5, A0A0A0MS75, A8MYS5, A8MZF5, B7Z2X5, E9PKT0, E9PQ19, E9PRZ2, H0YCQ4, H0YDC6, H0YDJ5, H0YDQ4, H0YEE9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the fatty acid remodeling steps of GPI-anchor maturation where the unsaturated acyl chain at sn-2 of inositol phosphate is replaced by a saturated stearoyl chain. May catalyze the second step of the fatty acid remodeling, by reacylating a lyso-GPI intermediate at sn-2 of inositol phosphate by a saturated chain. The fatty acid remodeling steps is critical for the integration of GPI-APs into lipid rafts.

Subunit / interactions. Interacts with PGAP2IP.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Ubiquitously expressed, with highest levels in testis and pancreas.

Disease relevance. Hyperphosphatasia with impaired intellectual development syndrome 3 (HPMRS3) [MIM:614207] An autosomal recessive disorder usually characterized by intellectual disability, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. This isoform is predicted to contain an additional transmembrane domain at position 85-105. If this domain exists, the topology of the protein would be modified, possibly challenging the GPI-anchor remodeling function of the protein.

Similarity. Belongs to the PGAP2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9UHJ9-1	2	yes
Q9UHJ9-2	1
Q9UHJ9-3	3
Q9UHJ9-4	4
Q9UHJ9-5	5

RefSeq proteins (20): NP_001138910, NP_001243164, NP_001243165, NP_001243166, NP_001243167, NP_001243168, NP_001243169, NP_001269967, NP_001269968, NP_001269969, NP_001333326, NP_001333327, NP_001333328, NP_001333329, NP_001333330, NP_001333331, NP_001333332, NP_001333333, NP_001333334, NP_055304* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019402	CWH43_N	Domain
IPR039545	PGAP2	Family

Pfam: PF10277

Catalyzed reactions (Rhea), 1 shown:

• [protein]-C-terminal carboxyl phosphoethanolamide-lysoGPI(deacylinositol-H7) + octadecanoyl-CoA = [protein]-C-terminal carboxyl phosphoethanolamide-(1-radyl,2-octadecanoyl)-GPI(deacylinositol-H7) + CoA (RHEA:83851)

UniProt features (24 total): topological domain 6, sequence variant 6, transmembrane region 5, splice variant 5, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHJ9-F1	90.00	0.73

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 315 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (1): GPI anchor biosynthetic process (GO:0006506)

GO Molecular Function (2): transferase activity (GO:0016740), protein binding (GO:0005515)

GO Cellular Component (6): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
GPI anchored protein biosynthesis	1
catalytic activity	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGAP2	PGAP3	Q96FM1	859
PGAP2	PIGO	Q8TEQ8	855
PGAP2	PIGV	Q9NUD9	844
PGAP2	PIGL	Q9Y2B2	843
PGAP2	PIGW	Q7Z7B1	817
PGAP2	PIGM	Q9H3S5	794
PGAP2	PIGT	Q969N2	791
PGAP2	PIGY	Q3MUY2	760
PGAP2	PIGK	Q92643	754
PGAP2	PGAP1	Q75T13	753
PGAP2	PIGN	O95427	713
PGAP2	PIGG	Q5H8A4	683
PGAP2	PIGA	P37287	676
PGAP2	PIGC	Q92535	642
PGAP2	PIGH	Q14442	626

IntAct

21 interactions, top by confidence:

A	B	Type	Score
PGAP2	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
	PGAP2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	PGAP2	psi-mi:“MI:0915”(physical association)	0.560
PGAP2	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
PGAP2	BRICD5	psi-mi:“MI:0915”(physical association)	0.400
PGAP2	CFTR	psi-mi:“MI:0915”(physical association)	0.370
Spcs2	SEC11A	psi-mi:“MI:0914”(association)	0.350
Cdk5rap2	TBC1D31	psi-mi:“MI:0914”(association)	0.350
PFKFB2		psi-mi:“MI:0914”(association)	0.350
Ppp6c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Ranbp1	VPS26C	psi-mi:“MI:0914”(association)	0.350
CFAP298	PLXNB1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
PGAP2	MESD	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), PGAP2 (Affinity Capture-MS), PGAP2 (Affinity Capture-MS), PGAP2 (Affinity Capture-MS), PGAP2 (Affinity Capture-MS), PGAP2 (Affinity Capture-MS), PGAP2 (Affinity Capture-MS), CREB3L1 (Two-hybrid), PGAP2 (Two-hybrid), PGAP2 (Two-hybrid), PGAP2 (Two-hybrid), PGAP2 (Two-hybrid), PGAP2 (Two-hybrid), PGAP2 (Two-hybrid)

ESM2 similar proteins: A2A559, A2V7M9, A6H7B8, A6X919, A7YWP2, A8KBG2, A8WFS8, B2GV22, D4AD75, E1BYA3, F1Q8R9, O08888, O45145, O49639, P25625, P38298, P70245, Q0VFE3, Q15125, Q290J8, Q2ABP2, Q2ABP3, Q3SZ36, Q3TQR0, Q568I2, Q5M9A7, Q60490, Q60WT2, Q68EV0, Q6P0S3, Q753H5, Q7K0P4, Q801D8, Q801G2, Q8C2R7, Q8N4S7, Q8R4X1, Q8T8L8, Q8TDN7, Q91VH1

Diamond homologs: A6H7B8, A8KBG2, A8XST1, Q22141, Q29M88, Q2ABP2, Q2ABP3, Q3TQR0, Q5BL33, Q5M9A7, Q9UHJ9, Q9VPT7, Q9VWK6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	10
Uncertain significance	72
Likely benign	33
Benign	18

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
4294005	NM_001256236.2(PGAP2):c.-60_-57del	Pathogenic
50502	NM_014489.4(PGAP2):c.479A>G (p.Tyr160Cys)	Pathogenic
50505	NM_014489.4(PGAP2):c.46C>T (p.Arg16Trp)	Pathogenic
50506	NM_014489.4(PGAP2):c.491C>T (p.Thr164Ile)	Pathogenic
694699	NM_014489.4(PGAP2):c.2T>G (p.Met1Arg)	Pathogenic
827783	NM_014489.4(PGAP2):c.391G>T (p.Glu131Ter)	Pathogenic
1678531	NM_014489.4(PGAP2):c.1A>G (p.Met1Val)	Likely pathogenic
2692369	NM_014489.4(PGAP2):c.737G>T (p.Arg246Leu)	Likely pathogenic
3731331	NM_014489.4(PGAP2):c.642_645del (p.Leu215fs)	Likely pathogenic
4074794	NM_014489.4(PGAP2):c.509A>G (p.Tyr170Cys)	Likely pathogenic
4849295	NM_014489.4(PGAP2):c.166-1G>C	Likely pathogenic
4849327	NM_014489.4(PGAP2):c.737G>A (p.Arg246Gln)	Likely pathogenic
522122	NM_014489.4(PGAP2):c.732dup (p.Gln245fs)	Likely pathogenic
633511	NM_014489.4(PGAP2):c.380C>T (p.Ala127Val)	Likely pathogenic
802653	NM_014489.4(PGAP2):c.449T>C (p.Phe150Ser)	Likely pathogenic
827784	NM_014489.4(PGAP2):c.881C>T (p.Thr294Met)	Likely pathogenic

SpliceAI

1811 predictions. Top by Δscore:

Variant	Effect	Δscore
11:3802542:A:T	donor_gain	1.0000
11:3824136:G:GG	donor_gain	1.0000
11:3824153:G:GT	donor_gain	1.0000
11:3824154:G:T	donor_gain	1.0000
11:3824164:G:T	donor_gain	1.0000
11:3825326:A:AG	acceptor_gain	1.0000
11:3825327:G:GA	acceptor_gain	1.0000
11:3825327:GT:G	acceptor_gain	1.0000
11:3802541:G:GT	donor_gain	0.9900
11:3808288:CAACA:C	acceptor_loss	0.9900
11:3808290:ACAG:A	acceptor_loss	0.9900
11:3808292:A:AG	acceptor_gain	0.9900
11:3808292:A:T	acceptor_loss	0.9900
11:3808293:G:GG	acceptor_gain	0.9900
11:3808293:GGTA:G	acceptor_gain	0.9900
11:3808866:GGGT:G	donor_gain	0.9900
11:3811401:G:GT	donor_gain	0.9900
11:3824102:G:GG	donor_gain	0.9900
11:3824129:G:GT	donor_gain	0.9900
11:3824164:G:GT	donor_gain	0.9900
11:3824374:G:GT	donor_gain	0.9900
11:3825321:A:AG	acceptor_gain	0.9900
11:3825322:C:G	acceptor_gain	0.9900
11:3825322:CAACA:C	acceptor_loss	0.9900
11:3825323:A:AG	acceptor_gain	0.9900
11:3825323:AACAG:A	acceptor_loss	0.9900
11:3825324:A:G	acceptor_gain	0.9900
11:3825325:CA:C	acceptor_loss	0.9900
11:3825326:AGT:A	acceptor_gain	0.9900
11:3825326:AGTG:A	acceptor_loss	0.9900

AlphaMissense

2068 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:3825339:T:C	F216L	1.000
11:3825341:T:A	F216L	1.000
11:3825341:T:G	F216L	1.000
11:3825381:T:C	F230L	1.000
11:3825383:C:A	F230L	1.000
11:3825383:C:G	F230L	1.000
11:3811369:G:A	C37Y	0.999
11:3811370:C:G	C37W	0.999
11:3811419:T:A	C54S	0.999
11:3811419:T:C	C54R	0.999
11:3811420:G:A	C54Y	0.999
11:3811420:G:C	C54S	0.999
11:3823891:T:A	N58K	0.999
11:3823891:T:G	N58K	0.999
11:3823899:C:A	P61H	0.999
11:3823907:A:C	S64R	0.999
11:3823908:G:A	S64N	0.999
11:3823909:C:A	S64R	0.999
11:3823909:C:G	S64R	0.999
11:3823946:T:A	W77R	0.999
11:3823946:T:C	W77R	0.999
11:3824275:C:A	H142N	0.999
11:3824275:C:G	H142D	0.999
11:3824287:T:C	F146L	0.999
11:3824289:C:A	F146L	0.999
11:3824289:C:G	F146L	0.999
11:3824296:T:C	F149L	0.999
11:3824298:C:A	F149L	0.999
11:3824298:C:G	F149L	0.999
11:3825043:A:C	K183N	0.999

dbSNP variants (sampled 300 via entrez): RS1000064885 (11:3799777 C>CGGG), RS1000184729 (11:3802567 C>T), RS1000198150 (11:3797733 G>A,C,T), RS1000224965 (11:3805298 G>C), RS1000361371 (11:3815965 A>G), RS1000583003 (11:3798184 A>G,T), RS1000632378 (11:3810124 TTCTC>T,TTC,TTCTCTC), RS1000652940 (11:3825917 T>A), RS1000788481 (11:3803809 G>A,T), RS1000802500 (11:3808169 T>C,G), RS1000834186 (11:3816448 C>G,T), RS1000853946 (11:3805020 C>A), RS1000894030 (11:3809742 C>G,T), RS1000968198 (11:3814893 T>G), RS1001003750 (11:3826118 A>G,T)

Disease associations

OMIM: gene MIM:615187 | disease phenotypes: MIM:614207, MIM:160565, MIM:185070, MIM:612783, MIM:308350, MIM:613227

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperphosphatasia with intellectual disability syndrome 3	Definitive	Autosomal recessive
hyperphosphatasia-intellectual disability syndrome	Supportive	Autosomal recessive

Mondo (9): hyperphosphatasia with intellectual disability syndrome 3 (MONDO:0013628), tubular aggregate myopathy (MONDO:0008051), Stormorken syndrome (MONDO:0008497), combined immunodeficiency due to STIM1 deficiency (MONDO:0013008), autism spectrum disorder (MONDO:0005258), genetic developmental and epileptic encephalopathy (MONDO:0100062), cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 (MONDO:0013188), omphalocele (MONDO:0019015), hyperphosphatasia-intellectual disability syndrome (MONDO:0016596)

Orphanet (8): Hyperphosphatasia-intellectual disability syndrome (Orphanet:247262), Combined immunodeficiency due to CRAC channel dysfunction (Orphanet:169090), Tubular aggregate myopathy (Orphanet:2593), Combined immunodeficiency due to STIM1 deficiency (Orphanet:317430), Stormorken-Sjaastad-Langslet syndrome (Orphanet:3204), Dysequilibrium syndrome (Orphanet:1766), Omphalocele (Orphanet:660), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

91 total (30 of 91 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000289	Broad philtrum
HP:0000303	Mandibular prognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000347	Micrognathia
HP:0000378	Cupped ear
HP:0000391	Thickened helices
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000565	Esotropia
HP:0000582	Upslanted palpebral fissure
HP:0000594	Shallow anterior chamber
HP:0000637	Long palpebral fissure

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C567690	Cerebellar Ataxia, Mental Retardation, And Dysequilibrium Syndrome 3 (supp.)
C557827	Immune dysfunction with T-cell inactivation due to calcium entry defect 2 (supp.)
C566108	Stormorken Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	2
Arsenic	affects expression, affects methylation, decreases expression, increases abundance	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
methylselenic acid	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression	1
Bilirubin	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Doxorubicin	decreases expression	1
Selenium	affects cotreatment, decreases expression, increases expression	1
Silicon Dioxide	decreases expression	1
Dronabinol	increases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Vitamin E	affects cotreatment, decreases expression	1
Sodium Selenite	decreases expression	1
Zinc Sulfate	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder