GMPPA

Summary

GMPPA (GDP-mannose pyrophosphorylase A, HGNC:22923) is a protein-coding gene on chromosome 2q35, encoding Mannose-1-phosphate guanylyltransferase regulatory subunit alpha (Q96IJ6). Regulatory subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex; reduces the catalytic activity of GMPPB when part of the complex.

This gene is thought to encode a GDP-mannose pyrophosphorylase. This enzyme catalyzes the reaction which converts mannose-1-phosphate and GTP to GDP-mannose which is involved in the production of N-linked oligosaccharides.

Source: NCBI Gene 29926 — RefSeq curated summary.

At a glance

• Gene–disease (curated): alacrima, achalasia, and intellectual disability syndrome (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 7 total
• Phenotypes (HPO): 63
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_013335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22923
Approved symbol	GMPPA
Name	GDP-mannose pyrophosphorylase A
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144591
Ensembl biotype	protein_coding
OMIM	615495
Entrez	29926

Gene structure

Transcript identifiers

Ensembl transcripts: 82 — 45 protein_coding, 18 retained_intron, 17 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000313597, ENST00000341142, ENST00000358215, ENST00000373908, ENST00000373917, ENST00000435316, ENST00000443704, ENST00000455657, ENST00000480034, ENST00000480506, ENST00000481170, ENST00000496536, ENST00000622191, ENST00000635609, ENST00000682058, ENST00000682102, ENST00000682340, ENST00000682435, ENST00000682443, ENST00000682481, ENST00000682488, ENST00000682576, ENST00000683106, ENST00000683131, ENST00000683203, ENST00000683241, ENST00000683382, ENST00000683386, ENST00000683402, ENST00000683591, ENST00000683598, ENST00000683617, ENST00000683626, ENST00000683691, ENST00000683746, ENST00000683752, ENST00000683864, ENST00000683946, ENST00000683964, ENST00000684227, ENST00000684242, ENST00000684274, ENST00000684334, ENST00000684412, ENST00000684562, ENST00000684669, ENST00000684706, ENST00000684729, ENST00000895885, ENST00000895886, ENST00000895887, ENST00000895888, ENST00000895889, ENST00000895890, ENST00000895891, ENST00000895892, ENST00000895893, ENST00000895894, ENST00000895895, ENST00000895896, ENST00000930365, ENST00000930366, ENST00000930367, ENST00000930368, ENST00000930369, ENST00000930370, ENST00000930371, ENST00000930372, ENST00000950497, ENST00000950498, ENST00000950499, ENST00000950500, ENST00000950501, ENST00000950502, ENST00000950503, ENST00000950504, ENST00000950505, ENST00000950506, ENST00000950507, ENST00000950508, ENST00000950509, ENST00000950510

RefSeq mRNA: 4 — MANE Select: NM_013335 NM_001374294, NM_001374295, NM_013335, NM_205847

CCDS: CCDS2441

Canonical transcript exons

ENST00000313597 — 13 exons

Exon	Start	End
ENSE00001884260	219498891	219498938
ENSE00002489925	219505228	219505362
ENSE00002499917	219505715	219505761
ENSE00002700431	219504083	219504213
ENSE00003466731	219505980	219506072
ENSE00003508971	219501851	219502037
ENSE00003518288	219500121	219500218
ENSE00003550109	219499956	219500015
ENSE00003634457	219502382	219502441
ENSE00003646260	219506254	219506422
ENSE00003654275	219501476	219501579
ENSE00003786905	219505458	219505555
ENSE00003900258	219506698	219506989

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.8456 / max 217.3038, expressed in 1816 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25515	33.8456	1816

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	95.33	gold quality
mucosa of transverse colon	UBERON:0004991	95.00	gold quality
apex of heart	UBERON:0002098	94.78	gold quality
adenohypophysis	UBERON:0002196	94.39	gold quality
tendon of biceps brachii	UBERON:0008188	94.37	gold quality
stromal cell of endometrium	CL:0002255	94.32	gold quality
right lobe of liver	UBERON:0001114	94.27	gold quality
pituitary gland	UBERON:0000007	94.05	gold quality
islet of Langerhans	UBERON:0000006	93.88	gold quality
pancreas	UBERON:0001264	93.21	gold quality
endocervix	UBERON:0000458	93.08	gold quality
right lobe of thyroid gland	UBERON:0001119	93.05	gold quality
rectum	UBERON:0001052	93.03	gold quality
granulocyte	CL:0000094	92.97	gold quality
body of stomach	UBERON:0001161	92.21	gold quality
ascending aorta	UBERON:0001496	92.20	gold quality
thoracic aorta	UBERON:0001515	92.13	gold quality
left lobe of thyroid gland	UBERON:0001120	91.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.76	gold quality
transverse colon	UBERON:0001157	91.75	gold quality
left coronary artery	UBERON:0001626	91.73	gold quality
minor salivary gland	UBERON:0001830	91.70	gold quality
ectocervix	UBERON:0012249	91.56	gold quality
saliva-secreting gland	UBERON:0001044	91.51	gold quality
left uterine tube	UBERON:0001303	91.39	gold quality
coronary artery	UBERON:0001621	91.39	gold quality
body of uterus	UBERON:0009853	91.32	gold quality
right atrium auricular region	UBERON:0006631	91.28	gold quality
right coronary artery	UBERON:0001625	91.25	gold quality
thyroid gland	UBERON:0002046	90.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting GMPPA, 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-7152-3P	99.97	67.47	849
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-4529-5P	96.74	65.77	569
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-4707-5P	90.95	65.69	110

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 3)

• GMPPA might serve as a GMPPB regulatory subunit mediating feedback inhibition of GMPPB instead of displaying catalytic enzyme activity itself. (PMID:24035193)
• Based on our findings and the previous report describing patients with an overlapping phenotype, we conclude that this novel variant in GMPPA, identified by exome sequencing in the proband and her affected sister, is the genetic cause of their phenotype and may expand the known phenotype of this recently described glycosylation disorder. (PMID:28574218)
• Evidence of GMPPA founder mutation in indigenous Guatemalan population associated with alacrima, achalasia, and mental retardation syndrome. (PMID:31898852)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gmppab	ENSDARG00000023498
danio_rerio	gmppaa	ENSDARG00000024112
mus_musculus	Gmppa	ENSMUSG00000033021
rattus_norvegicus	Gmppa	ENSRNOG00000019946
drosophila_melanogaster	Gmppa	FBGN0034035
caenorhabditis_elegans	Y47D9A.1	WBGENE00021628

Paralogs (3): EIF2B3 (ENSG00000070785), EIF2B5 (ENSG00000145191), GMPPB (ENSG00000173540)

Protein

Protein identifiers

Mannose-1-phosphate guanylyltransferase regulatory subunit alpha — Q96IJ6 (reviewed: Q96IJ6)

Alternative names: GDP-mannose pyrophosphorylase A, GTP-mannose-1-phosphate guanylyltransferase alpha

All UniProt accessions (15): Q96IJ6, A0A087WUI8, A0A0U1RRC2, A0A384MDS7, A0A804HID2, A0A804HIM4, A0A804HIS0, A0A804HJC3, A0A804HKA4, A0A804HLB2, A0A804HLK2, B4DJR0, C9J255, C9JAH0, F8WD54

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex; reduces the catalytic activity of GMPPB when part of the complex. Mediates allosteric feedback inhibition of GMPPB catalytic activity upon binding GDP-alpha-D-mannose. Together with GMPPB regulates GDP-alpha-D-mannose levels.

Subunit / interactions. Component of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex composed of 4 GMPPA subunits and 8 GMPPB subunits; the complex is organized into three layers, a central layer made up of 2 GMPPA dimers sandwiched between two layers each made up of 2 GMPPB dimers.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in fibroblasts (at protein level).

Disease relevance. Alacrima, achalasia, and impaired intellectual development syndrome (AAMR) [MIM:615510] An autosomal recessive disorder characterized by onset of alacrima, achalasia, and intellectual disability at birth or in early infancy. More variable features include hypotonia, gait abnormalities, anisocoria, and visual or hearing deficits. The disorder shows similarity to the triple A syndrome, but patients with AAMR do not have adrenal insufficiency. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal substrate-binding domain adopts a Rossman-like fold and has a binding pocket for GTP or GDP-alpha-D-mannose. The C-terminal domain consists of a series of tandem hexapeptide repeats that adopt a beta-helix conformation. The beta-helix forms several protein interaction surfaces involved in assembly of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex. A loop extending from the C-terminal domain (C-loop) is involved in interaction with other subunits of the GMPPA-GMPPB complex and may be involved in allosteric inhibition of GMPPB catalytic activity by GMPPA.

Similarity. Belongs to the transferase hexapeptide repeat family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IJ6-1	1	yes
Q96IJ6-2	2

RefSeq proteins (4): NP_001361223, NP_001361224, NP_037467, NP_995319 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005835	NTP_transferase_dom	Domain
IPR018357	Hexapep_transf_CS	Conserved_site
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR050486	Mannose-1P_guanyltransferase	Family
IPR056729	GMPPB_C	Domain

Pfam: PF00483, PF25087

UniProt features (70 total): strand 22, mutagenesis site 13, helix 11, sequence variant 7, turn 6, sequence conflict 4, region of interest 3, binding site 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7D73	ELECTRON MICROSCOPY	3
7D74	ELECTRON MICROSCOPY	3.1
7D72	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IJ6-F1	93.15	0.83

Functional residue map

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

Ligand- & substrate-binding residues (2): 85; 247

Mutagenesis-validated functional residues (13):

Position	Phenotype
85	reduces gdp-alpha-d-mannose binding affinity but does not affect assembly of gmppa-gmppb complex; when associated with a
99	does not disrupt the interaction with gmppb or other gmppa molecules.
100	does not disrupt the interaction with gmppb or other gmppa molecules.
247	reduces gdp-alpha-d-mannose binding affinity but does not affect assembly of gmppa-gmppb complex; when associated with k
247	does not instate mannose-1-phosphate guanylyltransferase catalytic activity.
318	disrupts the interaction with gmppb and other gmppa molecules.
350	disrupts the interaction with gmppb and other gmppa molecules and reduces the efficiency of gmppb allosteric inhibition;
352	disrupts the interaction with gmppb and other gmppa molecules and reduces the efficiency of gmppb allosteric inhibition;
362–365	reduces the interaction with gmppb and decreases efficiency of gmppb inhibition.
372	reduces the efficiency of gmppb allosteric inhibition.
372	disrupts the interaction with other gmppa molecules slightly but not with gmppb.
396	disrupts the interaction with other gmppa molecules but not with gmppb.
408	does not disrupt the interaction with gmppb or other gmppa molecules.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-446205	Synthesis of GDP-mannose

MSigDB gene sets: 252 (showing top): GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, GOBP_MUSCLE_ORGAN_MORPHOGENESIS, GOBP_NEURON_APOPTOTIC_PROCESS

GO Biological Process (16): glycoprotein metabolic process (GO:0009100), GDP-mannose biosynthetic process (GO:0009298), negative regulation of biosynthetic process (GO:0009890), GDP-mannose metabolic process (GO:0019673), telencephalon development (GO:0021537), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), negative regulation of phosphate metabolic process (GO:0045936), muscle organ morphogenesis (GO:0048644), cognition (GO:0050890), neuromuscular process (GO:0050905), neuron apoptotic process (GO:0051402), skeletal muscle organ development (GO:0060538), motor behavior (GO:0061744), negative regulation of small molecule metabolic process (GO:0062014), obsolete protein glycosylation (GO:0006486), biosynthetic process (GO:0009058)

GO Molecular Function (5): enzyme inhibitor activity (GO:0004857), transferase activity (GO:0016740), enzyme binding (GO:0019899), molecular sensor activity (GO:0140299), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), GDP-mannose pyrophosphorylase complex (GO:0120508)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of metabolic process	4
muscle organ development	2
nervous system process	2
catalytic activity	2
cellular anatomical structure	2
protein metabolic process	1
carbohydrate derivative metabolic process	1
phosphomannomutase activity	1
nucleotide-sugar biosynthetic process	1
GDP-mannose metabolic process	1
biosynthetic process	1
regulation of biosynthetic process	1
nucleotide-sugar metabolic process	1
forebrain development	1
anatomical structure development	1
nucleobase-containing compound metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
phosphate-containing compound metabolic process	1
animal organ morphogenesis	1
apoptotic process	1
behavior	1
small molecule metabolic process	1
regulation of small molecule metabolic process	1
metabolic process	1
enzyme regulator activity	1
molecular function inhibitor activity	1
protein binding	1
molecular function regulator activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1
transferase complex, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

1846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GMPPA	PMM2	O15305	621
GMPPA	MPI	P34949	582
GMPPA	PGM3	O95394	564
GMPPA	UGP2	Q16851	538
GMPPA	DPM1	O60762	533
GMPPA	PMM1	Q92871	500
GMPPA	CHPF	Q8IZ52	500
GMPPA	DPM2	O94777	484
GMPPA	DOLK	Q9UPQ8	483
GMPPA	GMDS	O60547	476
GMPPA	FCSK	Q8N0W3	474
GMPPA	KLHDC8A	Q8IYD2	471
GMPPA	MAN1B1	Q9UKM7	458
GMPPA	STT3B	Q8TCJ2	449
GMPPA	UGDH	O60701	435

IntAct

97 interactions, top by confidence:

A	B	Type	Score
GMPPA	GMPPB	psi-mi:“MI:0915”(physical association)	0.870
GMPPB	GMPPA	psi-mi:“MI:0915”(physical association)	0.870
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
GMPPA	BTC	psi-mi:“MI:0915”(physical association)	0.720
BTC	GMPPA	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GOLPH3	RCC1L	psi-mi:“MI:0914”(association)	0.640
DDAH2	EPB41L2	psi-mi:“MI:0914”(association)	0.640
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
CRP	GMPPA	psi-mi:“MI:0915”(physical association)	0.560
NCK1	GMPPA	psi-mi:“MI:0915”(physical association)	0.560
ZNF688	GMPPA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (72): GMPPA (Two-hybrid), GMPPA (Two-hybrid), GMPPA (Two-hybrid), GMPPA (Two-hybrid), GMPPA (Affinity Capture-MS), GMPPA (Affinity Capture-MS), GMPPA (Two-hybrid), GMPPA (Co-fractionation), LPP (Co-fractionation), GMPPA (Affinity Capture-MS), GMPPA (Affinity Capture-MS), GMPPA (Affinity Capture-MS), GMPPA (Affinity Capture-MS), GMPPA (Affinity Capture-MS), GMPPA (Affinity Capture-MS)

ESM2 similar proteins: A4TQV0, A4WFL3, A5GLA9, A7FNX3, A8GKU8, A9MTV2, B0CM52, B1JHX9, B1WT08, B1XLF1, B2IUY3, B2K6F9, B2T2Z5, B5F8Q2, B5XTQ9, B7K5U7, B7KDB8, B8HM61, C0Q0L0, C6DH77, I3LUP1, O60064, P30521, P30523, P52415, Q0AA25, Q0AAX8, Q0VFM6, Q1C1E1, Q1CDL5, Q1J021, Q31QN4, Q3MBJ4, Q3SH75, Q57IU0, Q5N3K9, Q5XIC1, Q664I4, Q66KG5, Q6CZK2

Diamond homologs: A2VD83, A3QMC8, B0CM52, B1L9R3, B9CM12, B9K6N9, I3LUP1, L7N6A5, O22287, O74484, O74624, O93827, P0C5I2, P0CO20, P0CO21, P26396, P37820, P41940, P74285, Q0P8J1, Q0P8J8, Q0VFM6, Q295Y7, Q2UJU5, Q2YDJ9, Q4I1Y5, Q4U3E8, Q54K39, Q58730, Q5B1J4, Q5XIC1, Q61S97, Q66KG5, Q68EQ1, Q68EY9, Q6BN12, Q6CCU3, Q6DBU5, Q6DKE9, Q6FRY2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1983 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219498929:G:GT	donor_gain	1.0000
2:219498945:G:GT	donor_gain	1.0000
2:219501560:GAGTT:G	donor_gain	1.0000
2:219501575:G:GG	donor_gain	1.0000
2:219502380:A:AG	acceptor_gain	1.0000
2:219502381:G:GG	acceptor_gain	1.0000
2:219502439:GAG:G	donor_gain	1.0000
2:219502440:AGGT:A	donor_loss	1.0000
2:219502442:G:A	donor_loss	1.0000
2:219502442:G:GG	donor_gain	1.0000
2:219502443:T:G	donor_loss	1.0000
2:219504077:CCTCA:C	acceptor_loss	1.0000
2:219504078:CTCA:C	acceptor_loss	1.0000
2:219504079:TCAGG:T	acceptor_loss	1.0000
2:219504080:CAGGT:C	acceptor_loss	1.0000
2:219504179:G:GT	donor_gain	1.0000
2:219504179:G:T	donor_gain	1.0000
2:219504190:GC:G	donor_gain	1.0000
2:219504203:GA:G	donor_gain	1.0000
2:219504204:A:T	donor_gain	1.0000
2:219504214:G:GG	donor_gain	1.0000
2:219505361:GG:G	donor_gain	1.0000
2:219505362:GG:G	donor_gain	1.0000
2:219505448:C:CA	acceptor_gain	1.0000
2:219505456:A:AG	acceptor_gain	1.0000
2:219505457:G:GG	acceptor_gain	1.0000
2:219505976:A:AG	acceptor_gain	1.0000
2:219505977:C:G	acceptor_gain	1.0000
2:219505977:CA:C	acceptor_loss	1.0000
2:219505978:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000626006 (2:219500772 G>A), RS1000629898 (2:219507070 AT>A), RS1001113930 (2:219503357 T>G), RS1001554213 (2:219499850 G>A), RS1001917076 (2:219498313 G>A,C), RS1001973468 (2:219500219 G>A,T), RS1002119517 (2:219504813 C>A,G,T), RS1002237220 (2:219496925 A>C,T), RS1002529264 (2:219501740 G>A), RS1002558819 (2:219501405 A>C,G), RS1002591477 (2:219501051 C>A), RS1002791077 (2:219507424 C>G,T), RS1003250569 (2:219498415 C>A,T), RS1003691178 (2:219505175 C>T), RS1004258989 (2:219503619 A>C)

Disease associations

OMIM: gene MIM:615495 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
alacrima, achalasia, and intellectual disability syndrome	Definitive	Autosomal recessive
triple-A syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
alacrima, achalasia, and intellectual disability syndrome	Definitive	AR

Mondo (2): alacrima, achalasia, and intellectual disability syndrome (MONDO:0014219), triple-A syndrome (MONDO:0009279)

Orphanet (0):

HPO phenotypes

63 total (30 of 63 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000448	Prominent nose
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000522	Alacrima
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000666	Horizontal nystagmus
HP:0000750	Delayed speech and language development
HP:0000846	Adrenal insufficiency
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001097	Keratoconjunctivitis sicca
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001278	Orthostatic hypotension
HP:0001290	Generalized hypotonia
HP:0001347	Hyperreflexia
HP:0001531	Failure to thrive in infancy
HP:0001611	Hypernasal speech

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536008	Achalasia Addisonianism Alacrimia syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Cyclosporine	increases expression	4
Valproic Acid	affects expression, increases expression	3
Arsenic	increases expression, affects cotreatment, increases abundance	2
Cisplatin	increases expression, decreases response to substance, affects cotreatment	2
Tunicamycin	increases expression	2
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
entinostat	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	increases expression	1
Zinc	increases expression	1
Mifepristone	decreases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

5 cell lines: 3 finite cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D3A5	GM28877	Finite cell line	Female
CVCL_D3A6	GM28880	Transformed cell line	Female
CVCL_D3A7	GM28882	Transformed cell line	Male
CVCL_D6Z0	GM28879	Finite cell line	Female
CVCL_D6Z1	GM28881	Finite cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02179801	Not specified	UNKNOWN	Screening Cardiovascular Patients for Aortic aNeurysms (SCAN)
NCT02393716	Not specified	TERMINATED	Endurant Evo US Clinical Trial
NCT02461524	Not specified	TERMINATED	Endurant Evo International Clinical Trial
NCT02485496	Not specified	TERMINATED	E-tegra Stent Graft System in the Treatment of Infra-renal Abdominal Aortic Aneurysms
NCT02692664	Not specified	COMPLETED	Prospective Multicenter Study for the Endovascular Treatment of Iliac Aneurysm With the Branched E-liac Stent Graft
NCT03407664	Not specified	UNKNOWN	NHS AAA Screening Programme Data Linkage With HES and ONS Datasets
NCT03762525	Not specified	COMPLETED	Iliac Branch Device Movement During Cardiac Cycle (IBD-dynamics)
NCT04080557	Not specified	COMPLETED	Abdominal Aortic Aneurysm Patients Remain at Risk for Delirium on the Surgical Ward After Intensive Care Unit Dismissal
NCT05064540	Not specified	RECRUITING	JAGUAR Trial: ObJective Analysis to GaUge EVAR Outcomes Through Randomization
NCT05133492	Not specified	ACTIVE_NOT_RECRUITING	First In Human Study for Small to Medium-sized Abdominal Aortic Aneurysm (AAA)
NCT05376514	Not specified	COMPLETED	Central Blood Pressure and Variability Evaluation
NCT05409118	Not specified	WITHDRAWN	JAGUAR Trial (Outside United States; OUS): ObJective Analysis to GaUge EVAR Outcomes Through Randomization