CRIPT

Summary

CRIPT (CXXC repeat containing interactor of PDZ3 domain, HGNC:14312) is a protein-coding gene on chromosome 2p21, encoding Cysteine-rich PDZ-binding protein (Q9P021). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies.

Source: NCBI Gene 9419 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Rothmund-Thomson syndrome type 3 (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 95 total — 10 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 34
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014171

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14312
Approved symbol	CRIPT
Name	CXXC repeat containing interactor of PDZ3 domain
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	HSPC139
Ensembl gene	ENSG00000119878
Ensembl biotype	protein_coding
OMIM	604594
Entrez	9419

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 nonsense_mediated_decay, 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000238892, ENST00000486447, ENST00000718244, ENST00000718245, ENST00000718246, ENST00000923190

RefSeq mRNA: 1 — MANE Select: NM_014171 NM_014171

CCDS: CCDS1829

Canonical transcript exons

ENST00000238892 — 5 exons

Exon	Start	End
ENSE00001169301	46624163	46630176
ENSE00001169308	46617215	46617298
ENSE00003540988	46623764	46623867
ENSE00004034501	46619627	46619681
ENSE00004034504	46618773	46618838

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.3647 / max 1152.3094, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20100	48.3647	1807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	96.81	gold quality
corpus epididymis	UBERON:0004359	95.72	gold quality
caput epididymis	UBERON:0004358	94.98	gold quality
cauda epididymis	UBERON:0004360	91.20	gold quality
cerebellar vermis	UBERON:0004720	89.77	gold quality
medial globus pallidus	UBERON:0002477	89.44	gold quality
superficial temporal artery	UBERON:0001614	89.39	gold quality
buccal mucosa cell	CL:0002336	89.11	gold quality
visceral pleura	UBERON:0002401	89.11	gold quality
trabecular bone tissue	UBERON:0002483	88.93	gold quality
penis	UBERON:0000989	88.89	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.74	gold quality
biceps brachii	UBERON:0001507	88.61	gold quality
amniotic fluid	UBERON:0000173	88.26	gold quality
globus pallidus	UBERON:0001875	88.17	gold quality
germinal epithelium of ovary	UBERON:0001304	87.94	gold quality
heart right ventricle	UBERON:0002080	87.94	gold quality
jejunum	UBERON:0002115	87.94	gold quality
cranial nerve II	UBERON:0000941	87.75	gold quality
jejunal mucosa	UBERON:0000399	87.38	gold quality
skin of hip	UBERON:0001554	87.33	gold quality
parietal pleura	UBERON:0002400	87.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.95	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.79	gold quality
spinal cord	UBERON:0002240	86.70	gold quality
esophagus squamous epithelium	UBERON:0006920	86.58	gold quality
pleura	UBERON:0000977	86.54	gold quality
mammary duct	UBERON:0001765	86.46	gold quality
epithelium of mammary gland	UBERON:0003244	86.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

272 targeting CRIPT, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-371B-5P	99.99	75.34	4759
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-196A-1-3P	99.99	72.15	2772
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 5)

• we describe a third patient with defects in the CRIPT gene responsible for short stature, microcephaly, and distinctive facies [MIM:615789]. The clinical presentation of our patient expands the phenotype of CRIPT mutations to include postnatal growth delay, distinct from primordial dwarfism. (PMID:27250922)
• The PSD-95 GK domain binds to Gnb5, and this interaction is triggered by CRIPT-derived PDZ3 ligands binding to the third PDZ domain of PSD-95, unraveling a hierarchical binding mechanism of PSD-95 complex formation. (PMID:30864948)
• Divergent Evolution of a Protein-Protein Interaction Revealed through Ancestral Sequence Reconstruction and Resurrection. (PMID:32750125)
• Mitotic spindle disassembly in human cells relies on CRIPT having hierarchical redox signals. (PMID:36148798)
• Biallelic variants in CRIPT cause a Rothmund-Thomson-like syndrome with increased cellular senescence. (PMID:37013901)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cript	ENSDARG00000102511
mus_musculus	Cript	ENSMUSG00000024146
rattus_norvegicus	Cript	ENSRNOG00000015215
drosophila_melanogaster	CG4537	FBGN0032153
caenorhabditis_elegans	C36B1.14	WBGENE00044614

Paralogs (2): POLR2C (ENSG00000102978), POLR1C (ENSG00000171453)

Protein

Protein identifiers

Cysteine-rich PDZ-binding protein — Q9P021 (reviewed: Q9P021)

Alternative names: Cysteine-rich interactor of PDZ three

All UniProt accessions (1): Q9P021

UniProt curated annotations — full annotation on UniProt →

Function. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Involved in the cytoskeletal anchoring of DLG4 in excitatory synapses.

Subunit / interactions. Component of the minor spliceosome. Within this complex, interacts with RNF113A, as well as with SF3B1/SF3b155, SF3B2/SF3b145 and PHF5A/SF3b14b. Interacts with TUBB1. Interacts strongly with the PDZ3 domain of members of the DLG4 family. Associates with microtubules. Interacts with DLG4.

Subcellular location. Cytoplasm. Synapse. Cell projection. Dendritic spine.

Disease relevance. Rothmund-Thomson syndrome 3 (RTS3) [MIM:615789] A form of Rothmund-Thomson syndrome, a disorder characterized by sparse hair, eyebrows and eyelashes, juvenile cataracts, and poikiloderma, a genodermatosis presenting with mottled pigmentation, telangiectasia and epidermal atrophy. Additional features are short stature, dysplastic nails, and skeletal and dental abnormalities. RTS3 is an autosomal recessive form. RTS3 patients also exhibit microcephaly, with moderate to severe neurodevelopmental delay and seizures. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CRIPT family.

RefSeq proteins (1): NP_054890* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019367	PDZ-binding_CRIPT	Family

Pfam: PF10235

UniProt features (15 total): strand 5, turn 4, region of interest 2, helix 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7DVQ	ELECTRON MICROSCOPY	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P021-F1	78.77	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 301 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_POSTSYNAPTIC_MEMBRANE_ORGANIZATION, GOBP_RNA_SPLICING, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, FUJII_YBX1_TARGETS_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN

GO Biological Process (6): mRNA processing (GO:0006397), RNA splicing (GO:0008380), cytoplasmic microtubule organization (GO:0031122), protein localization to microtubule (GO:0035372), regulation of postsynaptic density assembly (GO:0099151), regulation of postsynaptic density protein 95 clustering (GO:1902897)

GO Molecular Function (5): microtubule binding (GO:0008017), PDZ domain binding (GO:0030165), protein-containing complex binding (GO:0044877), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (11): spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), postsynaptic density (GO:0014069), dendrite (GO:0030425), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), glutamatergic synapse (GO:0098978), postsynaptic density, intracellular component (GO:0099092), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
regulation of postsynaptic density organization	2
binding	2
dendrite	2
mRNA metabolic process	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
protein localization to microtubule cytoskeleton	1
postsynaptic density assembly	1
regulation of postsynaptic specialization assembly	1
regulation of excitatory synapse assembly	1
postsynaptic density protein 95 clustering	1
regulation of protein localization to membrane	1
tubulin binding	1
protein domain specific binding	1
protein binding	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
asymmetric synapse	1
postsynaptic specialization	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
neuron spine	1
postsynapse	1
synapse	1
postsynaptic density	1
postsynaptic specialization, intracellular component	1
cell junction	1

Protein interactions and networks

STRING

710 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRIPT	DLG4	P78352	989
CRIPT	TMEM247	A6NEH6	690
CRIPT	ATP6V1E2	Q96A05	574
CRIPT	GRIN2A	Q12879	499
CRIPT	GRIA1	P42261	498
CRIPT	DLG3	Q92796	489
CRIPT	KCNA4	P22459	478
CRIPT	DLG1	Q12959	472
CRIPT	DLGAP1	P78335	447
CRIPT	TRIM67	Q6ZTA4	437
CRIPT	DLG2	Q15700	435
CRIPT	PSMD5	Q16401	424
CRIPT	TSNAX	Q99598	424
CRIPT	ANKH	Q9HCJ1	404
CRIPT	RBM18	Q96H35	401

IntAct

155 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
DLG4	CRIPT	psi-mi:“MI:0407”(direct interaction)	0.770
CRIPT	DLG4	psi-mi:“MI:0407”(direct interaction)	0.770
DLG1	CRIPT	psi-mi:“MI:0915”(physical association)	0.610
CRIPT	DLG1	psi-mi:“MI:0407”(direct interaction)	0.610
CRIPT	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CRIPT	Dlg3	psi-mi:“MI:0407”(direct interaction)	0.560
CRIPT	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.560
Dlg4	CRIPT	psi-mi:“MI:0407”(direct interaction)	0.560
Dlg3	CRIPT	psi-mi:“MI:0407”(direct interaction)	0.560
CRIPT	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
CRIPT	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CRIPT	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
CRIPT	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
CRIPT	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CRIPT	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
CRIPT	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (36): C1orf123 (Co-fractionation), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-MS), CRIPT (Affinity Capture-RNA), DLG1 (Reconstituted Complex), DLG4 (Reconstituted Complex)

ESM2 similar proteins: A1XQU3, G1SE28, G1SKF7, G1SZ12, O65743, O70333, P37108, P38666, P40590, P46301, P50888, P50914, P61122, P83731, P83732, Q2YGT9, Q3SZ12, Q3T0U2, Q3ZC66, Q42347, Q4R5C7, Q5RBX7, Q5RF04, Q5SQF8, Q5ZKB6, Q63507, Q66WF5, Q6F444, Q6P6G7, Q6QMZ4, Q6Y263, Q792Q4, Q7SDU2, Q862I1, Q8BP67, Q8GYL5, Q8ISQ3, Q8JGR4, Q90YU3, Q962T5

Diamond homologs: O70333, Q1WCC0, Q3ZC66, Q567Z6, Q5ZKB6, Q6NU28, Q792Q4, Q9P021

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	37.6×	2e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	35.8×	2e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	35.8×	2e-05
Long-term potentiation	5	31.3×	3e-05
Assembly and cell surface presentation of NMDA receptors	8	26.7×	1e-07
Neurexins and neuroligins	9	23.3×	5e-08
Protein-protein interactions at synapses	5	17.5×	5e-04
Regulation of lipid metabolism by PPARalpha	5	9.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	55.3×	9e-13
protein localization to synapse	6	43.8×	8e-07
receptor clustering	7	41.6×	1e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	33.0×	4e-07
cell-cell adhesion	11	10.6×	1e-06
protein-containing complex assembly	7	7.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	4
Uncertain significance	33
Likely benign	32
Benign	15

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
127249	NM_014171.6(CRIPT):c.133_134insGG (p.Ala45fs)	Pathogenic
127250	NM_014171.6(CRIPT):c.141del (p.Phe47fs)	Pathogenic
1343340	NM_014171.6(CRIPT):c.7_8del (p.Cys3fs)	Pathogenic
1445347	NM_014171.6(CRIPT):c.150T>A (p.Tyr50Ter)	Pathogenic
1971820	NM_014171.6(CRIPT):c.132dup (p.Ala45fs)	Pathogenic
221619	NM_014171.5(CRIPT):c.-422_17-582del	Pathogenic
3233412	NM_014171.6(CRIPT):c.227G>A (p.Cys76Tyr)	Pathogenic
3896326	NC_000002.11:g.(?46844353)(46846821_46850902)del	Pathogenic
625543	GRCh37/hg19 2p21(chr2:46844284-46844565)	Pathogenic
976761	NM_014171.6(CRIPT):c.132del (p.Ala45fs)	Pathogenic
1704565	NC_000002.11:g.(?46844310)(46844438_46845911)del	Likely pathogenic
1997112	NM_014171.6(CRIPT):c.82+1G>A	Likely pathogenic
2150415	NM_014171.6(CRIPT):c.83-1G>A	Likely pathogenic
221618	NM_014171.6(CRIPT):c.8G>A (p.Cys3Tyr)	Likely pathogenic

SpliceAI

585 predictions. Top by Δscore:

Variant	Effect	Δscore
2:46617299:G:GG	donor_gain	1.0000
2:46617304:T:G	donor_gain	1.0000
2:46618767:TAACA:T	acceptor_loss	1.0000
2:46618770:CA:C	acceptor_loss	1.0000
2:46618771:A:AG	acceptor_gain	1.0000
2:46618771:A:G	acceptor_loss	1.0000
2:46618772:G:GG	acceptor_gain	1.0000
2:46618834:CACAG:C	donor_loss	1.0000
2:46618835:ACAGG:A	donor_loss	1.0000
2:46618836:CAGGT:C	donor_loss	1.0000
2:46618837:AG:A	donor_loss	1.0000
2:46618838:GG:G	donor_loss	1.0000
2:46618839:G:GA	donor_loss	1.0000
2:46619619:T:TA	acceptor_gain	1.0000
2:46619622:TACA:T	acceptor_loss	1.0000
2:46619623:ACAG:A	acceptor_loss	1.0000
2:46619624:CA:C	acceptor_loss	1.0000
2:46619625:A:AG	acceptor_gain	1.0000
2:46619626:G:GG	acceptor_gain	1.0000
2:46619626:G:GT	acceptor_loss	1.0000
2:46619626:GAAA:G	acceptor_gain	1.0000
2:46619677:GCAAG:G	donor_gain	1.0000
2:46619681:GG:G	donor_loss	1.0000
2:46619682:G:GG	donor_loss	1.0000
2:46619683:T:A	donor_loss	1.0000
2:46617297:AT:A	donor_gain	0.9900
2:46617298:TGTG:T	donor_loss	0.9900
2:46617299:G:C	donor_loss	0.9900
2:46617300:TGAG:T	donor_loss	0.9900
2:46618768:A:AG	acceptor_gain	0.9900

AlphaMissense

664 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:46618813:G:C	W19C	0.999
2:46618813:G:T	W19C	0.999
2:46623798:T:C	C58R	0.999
2:46623807:T:A	C61S	0.999
2:46623807:T:C	C61R	0.999
2:46623808:G:A	C61Y	0.999
2:46623808:G:C	C61S	0.999
2:46623843:T:A	C73S	0.999
2:46623843:T:C	C73R	0.999
2:46623844:G:A	C73Y	0.999
2:46623844:G:C	C73S	0.999
2:46623845:C:G	C73W	0.999
2:46623852:T:C	C76R	0.999
2:46623856:C:A	A77D	0.999
2:46624168:T:C	C83R	0.999
2:46624169:G:A	C83Y	0.999
2:46624170:T:G	C83W	0.999
2:46624181:G:A	G87E	0.999
2:46624181:G:T	G87V	0.999
2:46618811:T:A	W19R	0.998
2:46618811:T:C	W19R	0.998
2:46623798:T:A	C58S	0.998
2:46623799:G:A	C58Y	0.998
2:46623799:G:C	C58S	0.998
2:46623800:T:G	C58W	0.998
2:46623808:G:T	C61F	0.998
2:46623809:T:G	C61W	0.998
2:46623844:G:T	C73F	0.998
2:46623852:T:A	C76S	0.998
2:46623853:G:A	C76Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000111389 (2:46626998 A>G), RS1000839661 (2:46619008 A>G), RS1000896622 (2:46615330 G>A,C), RS1000900387 (2:46617931 C>G), RS1001014131 (2:46622916 G>A), RS1001065561 (2:46628335 C>G,T), RS1001132784 (2:46625732 A>C,G,T), RS1001361820 (2:46623211 G>C,T), RS1001584698 (2:46616244 G>C,T), RS1001699347 (2:46620794 G>A,T), RS1001752170 (2:46625973 G>A,C), RS1001778339 (2:46619526 A>G), RS1001854402 (2:46617197 G>A,C), RS1001905103 (2:46617073 A>G), RS1001961384 (2:46622135 C>A,T)

Disease associations

OMIM: gene MIM:604594 | disease phenotypes: MIM:615789, MIM:262400

GenCC curated gene-disease

Disease	Classification	Inheritance
Rothmund-Thomson syndrome type 3	Strong	Autosomal recessive

Mondo (2): Rothmund-Thomson syndrome type 3 (MONDO:0014347), isolated growth hormone deficiency type IA (MONDO:0009876)

Orphanet (2): Isolated growth hormone deficiency type IA (Orphanet:231662), Non-acquired isolated growth hormone deficiency (Orphanet:631)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000308	Microretrognathia
HP:0000348	High forehead
HP:0000463	Anteverted nares
HP:0000506	Telecanthus
HP:0000520	Proptosis
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0000938	Osteopenia
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001762	Talipes equinovarus
HP:0001903	Anemia
HP:0002007	Frontal bossing
HP:0002079	Hypoplasia of the corpus callosum
HP:0002209	Sparse scalp hair
HP:0002384	Focal impaired awareness seizure
HP:0002719	Recurrent infections
HP:0003510	Severe short stature
HP:0003577	Congenital onset
HP:0004325	Decreased body weight
HP:0004823	Anisopoikilocytosis
HP:0005280	Depressed nasal bridge
HP:0005585	Spotty hyperpigmentation
HP:0005590	Spotty hypopigmentation
HP:0009623	Proximal placement of thumb
HP:0009882	Short distal phalanx of finger

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000839_4	Height	3.000000e-07
GCST002310_1	Pulse pressure (alcohol consumption interaction)	8.000000e-07
GCST002310_3	Pulse pressure (alcohol consumption interaction)	1.000000e-06
GCST004070_3	Cerebrospinal P-tau181p levels	2.000000e-06
GCST007576_164	Chronotype	6.000000e-10
GCST010697_51	Cortical surface area (min-P)	4.000000e-12
GCST010698_64	Subcortical volume (min-P)	3.000000e-09
GCST010699_93	Brain morphology (min-P)	1.000000e-12
GCST010700_22	Cortical thickness (MOSTest)	9.000000e-11
GCST010701_108	Cortical surface area (MOSTest)	4.000000e-12
GCST010702_134	Subcortical volume (MOSTest)	2.000000e-14
GCST010703_146	Brain morphology (MOSTest)	5.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0005763	pulse pressure measurement
EFO:0004763	p-tau measurement
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537404	Pituitary dwarfism 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric oxide	increases expression	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
corosolic acid	decreases expression	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Diethylstilbestrol	increases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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