NPPC

Summary

NPPC (natriuretic peptide C, HGNC:7941) is a protein-coding gene on chromosome 2q37.1, encoding C-type natriuretic peptide (P23582). Hormone which plays a role in endochondral ossification through regulation of cartilaginous growth plate chondrocytes proliferation and differentiation.

This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the cardiac natriuretic peptides CNP-53, CNP-29 and CNP-22, which belong to the natriuretic family of peptides. The encoded peptides exhibit vasorelaxation activity in laboratory animals and elevated levels of CNP-22 have been observed in the plasma of chronic heart failure patients.

Source: NCBI Gene 4880 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short stature with nonspecific skeletal abnormalities 1 (Limited, GenCC)
• GWAS associations: 21
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_024409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7941
Approved symbol	NPPC
Name	natriuretic peptide C
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	CNP
Ensembl gene	ENSG00000163273
Ensembl biotype	protein_coding
OMIM	600296
Entrez	4880

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000295440, ENST00000409852, ENST00000968048, ENST00000968049, ENST00000968050

RefSeq mRNA: 1 — MANE Select: NM_024409 NM_024409

CCDS: CCDS2489

Canonical transcript exons

ENST00000409852 — 3 exons

Exon	Start	End
ENSE00001582579	231926160	231926396
ENSE00001583675	231921809	231922315
ENSE00001584034	231925405	231925715

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 82.72.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8861 / max 185.9596, expressed in 461 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34544	2.8861	461

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.72	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	71.95	gold quality
prefrontal cortex	UBERON:0000451	71.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.19	gold quality
apex of heart	UBERON:0002098	70.80	gold quality
anterior cingulate cortex	UBERON:0009835	70.79	gold quality
cingulate cortex	UBERON:0003027	70.70	gold quality
spinal cord	UBERON:0002240	68.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.56	gold quality
heart left ventricle	UBERON:0002084	66.52	gold quality
hypothalamus	UBERON:0001898	66.10	gold quality
vermiform appendix	UBERON:0001154	65.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.94	gold quality
cardiac ventricle	UBERON:0002082	65.65	gold quality
right frontal lobe	UBERON:0002810	65.11	gold quality
esophagus mucosa	UBERON:0002469	64.33	gold quality
cerebellar cortex	UBERON:0002129	64.25	gold quality
cerebellar hemisphere	UBERON:0002245	64.15	gold quality
putamen	UBERON:0001874	63.95	gold quality
neocortex	UBERON:0001950	63.90	gold quality
frontal cortex	UBERON:0001870	63.64	gold quality
amygdala	UBERON:0001876	62.79	gold quality
cerebellum	UBERON:0002037	62.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	62.05	gold quality
cerebral cortex	UBERON:0000956	61.58	gold quality
right atrium auricular region	UBERON:0006631	61.45	gold quality
cardiac atrium	UBERON:0002081	60.46	gold quality
caecum	UBERON:0001153	60.36	gold quality
heart	UBERON:0000948	60.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, LEF1, TSC22D1

miRNA regulators (miRDB)

38 targeting NPPC, 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-5692A	100.00	74.40	6850
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-7977	98.65	66.18	2590

Literature-anchored findings (GeneRIF, showing 40)

• findings demonstrate that CNP metabolism is altered in patients with nephrotic syndrome and support the hypothesis that activation of renal CNP can be partially offset by a low-protein diet (PMID:12167597)
• CNP G2628A polymorphism made an even greater contribution to hypertension in the younger subpopulation. (PMID:12452325)
• human pro-CNP processing requires furin (PMID:12736257)
• Particulate guanylate cyclase activation by CNP induces a post-transductional down-regulation of soluble guanylate cyclase by a mechanism involving PKG and the proteasome pathway (PMID:14654233)
• The first intron in the CNP sequence does not contain any additional enhancer-binding sites. However, the signal sequence is indispensable for secretion of CNP and its appropriate physiological function. (PMID:15231517)
• BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction (PMID:15598085)
• discussion of C-type natriuretic peptide and guanylyl cyclase B receptor [review] (PMID:15911070)
• NT-proCNP may have a role in growth velocity and bone formation (PMID:16006435)
• CNP is capable of autoregulating the expression of its cognate receptor. (PMID:16109786)
• CNP is a modulator of acute inflammation in the blood vessel wall characterized by leukocyte and platelet activation, mediated, at least in part, via suppression of P-selectin expression. (PMID:16179391)
• report suggests that in humans, platelet-derived growth factor(PDGF) and downstream activation of protein kinase C could represent an important control for natriuretic peptide precursor C expression in vascular smooth muscle (PMID:16777970)
• There is a discordant expression of NPPC in newborn infants of mothers with type 1 diabetes. (PMID:17289171)
• The myocardium regularly produces CNP in patients with normal left ventricular systolic function. This is unchanged by brief periods of pacing, paroxysmal supraventricular tachycardia , or electrophysiological techniques. (PMID:17487764)
• Aortic valve stenosis is characterized by distinct downregulation of the gene expression of C-type natriuretic peptide. (PMID:17709640)
• Ostn is a naturally occurring ligand of the NPR-C clearance receptor and may act to locally modulate the actions of the natriuretic system in bone by blocking the clearance action of NPR-C, thus locally elevating levels of C-type natriuretic peptide. (PMID:17951249)
• NT-proANP & NT-proCNP showed high values in the first days of life followed by an initial sharp decrease and later by a progressive decrease until a plateau was reached (PMID:18280250)
• Changes in CNP plasma concentration after physical training might reflect an improvement in endothelial function in heart failure patients. (PMID:18391643)
• CNP was not altered following passive containment surgery in heart failure patients with dilated cardiomyopathy. (PMID:19008326)
• ProCNP-derived peptides are present in human prostate cancer. (PMID:19161538)
• CNP overproduction has been correlated to the skeletal overgrowth phenotype (PMID:19293575)
• results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height. (PMID:19570815)
• Data show that differences in magnitude and direction of transorgan gradients for CNP compared with NT-proCNP suggest net generalized cosecretion with differing mechanisms of clearance. (PMID:19620509)
• The study indicates functional signaling by B- and C-type natriuretic peptides in vascular endothelial cells, supporting possible roles of these mediators in regulating endothelial cell function. (PMID:20085572)
• Our data demonstrates that generation of CNP is not enhanced under heart failure condition like Chagas disease; CNP rise by severe HF is caused by its less degradation that is independent of neutral endopeptidase activity (PMID:20090473)
• NT-proCNP was associated with the endosteal apposition of bone at the distal forearm in females with a persistent eating disorder (PMID:20551602)
• Data suggest that decreased plasma proCNP concentration in idiopathic intracranial hypertension may reflect endothelial dysregulation of vascular tone and may be a marker in this disease. (PMID:20553977)
• The data indicates that ANP, BNP, and CNP and natriuretic peptide receptor transcripts are expressed and are functional in human lens epithelial cells. (PMID:20700369)
• CNP/NPR-B signaling pathway is activated during TGF-beta1 induced chondrogenic differentiation of human trabecular bone-derived mesenchymal stem cells. (PMID:20721606)
• new proCNP assay shows that proCNP is abundantly present in human seminal plasma and that seminal proCNP is secreted from the prostate gland and/or the seminal vesicles. (PMID:20797397)
• Results support role of TSC22D1 as an enhancer of CNP transcription and suggest that TGF-beta-induced upregulation of CNP expression in smooth muscle may be mediated in part by increased transcription of TSC22D1. (PMID:20802130)
• 56-year-old woman with Budd-Chiari syndrome who underwent liver transplantaation in whom heart failure was successfully managed using serial monitoring of BNP concentrations. (PMID:20832589)
• The concentrations of amino-terminal pro-C-type natriuretic peptide in rheumatoid arthritis patients were significantly increased when compared to healthy controls. (PMID:20934962)
• Continuous intravenous infusion of C-type natriuretic peptide did not attenuate the development of pulmonary hypertension caused by hypoxia and VEGF receptor blockade. (PMID:21820448)
• Serum NT-proCNP is elevated in advanced liver diseases and has prognostic value in cirrhotic patients. (PMID:22285383)
• Report the presence of CNP and its receptors, NPR2/3 in atherosclerotic plaques of human carotid artery. (PMID:22421372)
• CNP synthesis (as measured by NTproCNP levels in plasma) is closely related to linear growth in healthy children at all ages. We propose NTproCNP as a biomarker of linear growth. (PMID:22435455)
• NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis. (PMID:22645228)
• Gene expression of C-type natriuretic peptide and of its specific receptor NPR-B in human leukocytes of healthy and heart failure subjects (PMID:22884919)
• CNP production and clearance are increased in boys with Klinefelter syndrome. (PMID:22962429)
• these observations suggest that CNP and its specific receptor, NPR-B, can play a very important role in regulating cardiac hypertrophy and remodeling, indicating NPR-B as a new potential drug target for the treatment of cardiovascular disease. (PMID:23262354)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nppcl	ENSDARG00000043460
danio_rerio	nppcl2	ENSDARG00000116713
mus_musculus	Nppc	ENSMUSG00000026241
rattus_norvegicus	Nppc	ENSRNOG00000018854

Protein

Protein identifiers

C-type natriuretic peptide — P23582 (reviewed: P23582)

All UniProt accessions (1): P23582

UniProt curated annotations — full annotation on UniProt →

Function. Hormone which plays a role in endochondral ossification through regulation of cartilaginous growth plate chondrocytes proliferation and differentiation. May also be vasoactive and natriuretic. Acts by specifically binding and stimulating NPR2 to produce cGMP. Binds the clearance receptor NPR3.

Subcellular location. Secreted.

Tissue specificity. In the kidney, predominantly expressed in the distal tubular cells (at protein level).

Post-translational modifications. Degraded by IDE (in vitro).

Similarity. Belongs to the natriuretic peptide family.

RefSeq proteins (1): NP_077720* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000663	Natr_peptide	Family
IPR002406	C_natriurtcpep	Family
IPR030480	Natr_peptide_CS	Conserved_site

Pfam: PF00212

UniProt features (10 total): peptide 3, compositionally biased region 2, signal peptide 1, propeptide 1, region of interest 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1JDP	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23582-F1	63.71	0.11

Functional residue map

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

Disulfide bonds (1): 110–126

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5578768	Physiological factors
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 595 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_DIGESTION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, MYOGENIN_Q6, MODULE_274, GOBP_BEHAVIOR, GOBP_CARTILAGE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (42): ossification (GO:0001503), angiogenesis (GO:0001525), cumulus cell differentiation (GO:0001549), response to hypoxia (GO:0001666), blood vessel remodeling (GO:0001974), response to ischemia (GO:0002931), growth plate cartilage chondrocyte differentiation (GO:0003418), growth plate cartilage chondrocyte proliferation (GO:0003419), cGMP biosynthetic process (GO:0006182), protein folding (GO:0006457), intracellular calcium ion homeostasis (GO:0006874), receptor guanylyl cyclase signaling pathway (GO:0007168), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), post-embryonic development (GO:0009791), obsolete positive regulation of cGMP-mediated signaling (GO:0010753), obsolete cGMP-mediated signaling (GO:0019934), negative regulation of collagen biosynthetic process (GO:0032966), gastric emptying (GO:0035483), regulation of multicellular organism growth (GO:0040014), negative regulation of neuron apoptotic process (GO:0043524), response to ethanol (GO:0045471), positive regulation of osteoblast differentiation (GO:0045669), regulation of smooth muscle cell proliferation (GO:0048660), response to axon injury (GO:0048678), chromosome organization (GO:0051276), negative regulation of meiotic cell cycle (GO:0051447), c-di-GMP signaling (GO:0061939), multicellular organismal locomotion (GO:0071965), response to oxygen-glucose deprivation (GO:0090649), blood vessel diameter maintenance (GO:0097746), negative regulation of oocyte maturation (GO:1900194), meiotic cell cycle process involved in oocyte maturation (GO:1903537), cellular response to glycoprotein (GO:1904588), negative regulation of DNA biosynthetic process (GO:2000279), ovarian follicle development (GO:0001541), response to wounding (GO:0009611), response to decreased oxygen levels (GO:0036293), animal organ development (GO:0048513), oocyte development (GO:0048599)

GO Molecular Function (4): signaling receptor binding (GO:0005102), hormone activity (GO:0005179), hormone receptor binding (GO:0051427), guanylate cyclase activator activity (GO:0030250)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), secretory granule (GO:0030141), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cardiac conduction	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	2
response to stress	2
growth plate cartilage development	2
cell population proliferation	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
antral ovarian follicle growth	1
developmental process involved in reproduction	1
fused antrum stage	1
granulosa cell differentiation	1
response to decreased oxygen levels	1
tissue remodeling	1
chondrocyte differentiation involved in endochondral bone morphogenesis	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cGMP metabolic process	1
cellular process	1
protein maturation	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
enzyme-linked receptor protein signaling pathway	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to chemical	1
multicellular organism development	1
negative regulation of biosynthetic process	1
negative regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
gastric motility	1
multicellular organism growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1
protein binding	1
receptor ligand activity	1
signaling receptor binding	1
guanylate cyclase activity	1
cyclase activator activity	1
guanylate cyclase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPPC	NPR2	P20594	999
NPPC	NPR3	P17342	991
NPPC	NPPA	P01160	984
NPPC	NPR1	P16066	940
NPPC	NPPB	P16860	903
NPPC	FGFR3	P22607	764
NPPC	OSTN	P61366	712
NPPC	STK16	O75716	651
NPPC	SHOX	O15266	641
NPPC	AGT	P01019	636
NPPC	ADGRD1	Q6QNK2	633
NPPC	IHH	Q14623	613
NPPC	ACE	P12821	606
NPPC	MME	P08473	594
NPPC	COL2A1	P02458	593

IntAct

0 interactions, top by confidence:

BioGRID (14): NPPC (Affinity Capture-MS), NPPC (Affinity Capture-MS), NPPC (Affinity Capture-MS), NPPC (Affinity Capture-MS), NPPC (Affinity Capture-MS), NPPC (Synthetic Lethality), NPPC (Reconstituted Complex), NPPC (Reconstituted Complex), NPPC (Affinity Capture-MS), NPPC (Reconstituted Complex), NPPC (Reconstituted Complex), NPPC (Reconstituted Complex), NPPC (Reconstituted Complex), NPPC (Reconstituted Complex)

ESM2 similar proteins: B0VXV8, B8K1V9, D1MZV3, D5J9S0, D9IX97, O46540, O77559, P01021, P01142, P01143, P01160, P05125, P06296, P07499, P0C7P5, P0C7P6, P12272, P13085, P16860, P18104, P22858, P23582, P27596, P52211, P55206, P55207, P56283, P56469, P61312, P68515, P79799, P83228, P84715, P97297, Q09GK2, Q27J49, Q2PE51, Q2XXL8, Q61839, Q62949

Diamond homologs: A8S6B3, B0VXV8, B3EWY2, B3EWY3, B8K1V9, C6EVG7, D1MZV3, D9IX97, F5CPE8, P09196, P0C7P5, P0C7P6, P0CV87, P0DKY6, P18104, P18908, P21805, P22642, P23582, P55206, P55207, P56283, P79799, P82972, P83224, P83225, P83226, P83227, P83228, P83229, P83230, P83231, P83964, P84715, Q09GK2, Q1ZYW0, Q1ZYW1, Q27J49, Q2PE51, Q3SAE5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TSC22D1	“up-regulates quantity by expression”	NPPC	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	14
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

395 predictions. Top by Δscore:

Variant	Effect	Δscore
2:231926155:CCCA:C	donor_loss	1.0000
2:231926157:CA:C	donor_loss	1.0000
2:231925404:CCG:C	donor_gain	0.9900
2:231925716:C:CA	acceptor_loss	0.9900
2:231925721:C:T	acceptor_gain	0.9900
2:231925403:A:AC	donor_gain	0.9800
2:231925404:C:CC	donor_gain	0.9800
2:231925716:C:CC	acceptor_gain	0.9800
2:231925721:C:CT	acceptor_gain	0.9800
2:231925722:G:T	acceptor_gain	0.9800
2:231925150:C:CT	donor_gain	0.9700
2:231925403:ACCG:A	donor_gain	0.9700
2:231925404:CCGC:C	donor_gain	0.9700
2:231926158:A:AC	donor_gain	0.9700
2:231926159:C:CC	donor_gain	0.9700
2:231926159:CCTT:C	donor_gain	0.9700
2:231925156:AG:A	donor_gain	0.9600
2:231925397:GTAC:G	donor_loss	0.9600
2:231925398:TACT:T	donor_loss	0.9600
2:231925399:AC:A	donor_loss	0.9600
2:231925400:C:CA	donor_loss	0.9600
2:231925401:T:TA	donor_loss	0.9600
2:231925402:CA:C	donor_loss	0.9600
2:231922314:TC:T	acceptor_gain	0.9500
2:231922315:CC:C	acceptor_gain	0.9500
2:231925711:GGGAC:G	acceptor_gain	0.9500
2:231926156:CCACC:C	donor_gain	0.9500
2:231922312:GATCC:G	acceptor_loss	0.9400
2:231922313:ATCCT:A	acceptor_loss	0.9400
2:231922314:TCCT:T	acceptor_loss	0.9400

AlphaMissense

779 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:231925473:G:C	F111L	1.000
2:231925473:G:T	F111L	1.000
2:231925475:A:G	F111L	1.000
2:231925430:A:G	C126R	0.999
2:231925432:C:T	G125E	0.999
2:231925453:A:C	I118S	0.999
2:231925453:A:T	I118N	0.999
2:231925474:A:C	F111C	0.999
2:231925477:C:G	C110S	0.999
2:231925478:A:G	C110R	0.999
2:231925478:A:T	C110S	0.999
2:231925428:A:C	C126W	0.998
2:231925429:C:G	C126S	0.998
2:231925429:C:T	C126Y	0.998
2:231925430:A:T	C126S	0.998
2:231925433:C:G	G125R	0.998
2:231925433:C:T	G125R	0.998
2:231925440:G:C	S122R	0.998
2:231925440:G:T	S122R	0.998
2:231925441:C:A	S122I	0.998
2:231925442:T:G	S122R	0.998
2:231925456:C:G	R117P	0.998
2:231925459:T:A	D116V	0.998
2:231925464:C:A	K114N	0.998
2:231925464:C:G	K114N	0.998
2:231925474:A:G	F111S	0.998
2:231925475:A:T	F111I	0.998
2:231925476:G:C	C110W	0.998
2:231925477:C:A	C110F	0.998
2:231925477:C:T	C110Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000111951 (2:231922658 C>T), RS1000167130 (2:231926563 G>A,T), RS1000502802 (2:231924393 G>T), RS1001293051 (2:231923376 G>T), RS1001346426 (2:231923641 G>A), RS1001659728 (2:231927067 GTGTT>G), RS1002050753 (2:231926826 C>T), RS1002612023 (2:231928078 G>A,T), RS1002968220 (2:231924918 G>T), RS1002971988 (2:231922443 G>A), RS1003019828 (2:231927786 A>G), RS1003020240 (2:231925358 C>G,T), RS1003303798 (2:231926547 C>G), RS1003464109 (2:231923560 AAAT>A), RS1003992075 (2:231923172 T>C)

Disease associations

OMIM: gene MIM:600296 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
short stature with nonspecific skeletal abnormalities 1	Limited	Autosomal dominant

Mondo (1): short stature with nonspecific skeletal abnormalities 1 (MONDO:0014551)

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000175_5	Height	1.000000e-06
GCST000431_1	Height	3.000000e-09
GCST000817_107	Height	6.000000e-22
GCST002647_83	Height	2.000000e-26
GCST002702_36	Height	8.000000e-39
GCST004562_16	Waist circumference adjusted for body mass index	1.000000e-10
GCST004562_73	Waist circumference adjusted for body mass index	3.000000e-10
GCST004562_87	Waist circumference adjusted for body mass index	3.000000e-10
GCST004563_153	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	6.000000e-11
GCST004563_64	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-10
GCST004563_80	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	4.000000e-10
GCST004564_30	Waist circumference adjusted for BMI in active individuals	1.000000e-09
GCST004564_31	Waist circumference adjusted for BMI in active individuals	2.000000e-08
GCST004564_32	Waist circumference adjusted for BMI in active individuals	5.000000e-09
GCST010002_411	Refractive error	1.000000e-123
GCST012226_201	Waist circumference adjusted for body mass index	4.000000e-13
GCST012227_1245	Hip circumference adjusted for BMI	8.000000e-09
GCST012227_1246	Hip circumference adjusted for BMI	5.000000e-08
GCST012227_1247	Hip circumference adjusted for BMI	3.000000e-10
GCST90020028_717	Hip circumference adjusted for BMI	6.000000e-10
GCST90020028_718	Hip circumference adjusted for BMI	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases reaction	2
Estradiol	increases expression, decreases reaction	2
Aflatoxin B1	increases expression	2
Genistein	decreases reaction, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	decreases reaction, increases expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
pentanal	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
Poly(amidoamine)	increases expression	1
bisphenol S	increases expression, decreases reaction	1
MT19c compound	decreases expression	1
Resveratrol	increases expression, increases reaction	1
Fulvestrant	decreases reaction, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	decreases reaction, increases expression	1
Fonofos	increases methylation	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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