CSH1

Summary

CSH1 (chorionic somatomammotropin hormone 1, HGNC:2440) is a protein-coding gene on chromosome 17q23.3, encoding Chorionic somatomammotropin hormone 1 (P0DML2). Produced only during pregnancy and is involved in stimulating lactation, fetal growth and metabolism.

The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones and plays an important role in growth control. The gene is located at the growth hormone locus on chromosome 17 along with four other related genes in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. Although the five genes share a remarkably high degree of sequence identity, they are expressed selectively in different tissues. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed mainly in the placenta and utilizes multiple transcription initiation sites. Expression of the identical mature proteins for chorionic somatomammotropin hormones 1 and 2 is upregulated during development, although the ratio of 1 to 2 increases by term. Mutations in this gene result in placental lactogen deficiency and Silver-Russell syndrome.

Source: NCBI Gene 1442 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 38 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈16% of expected missense variation)
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.21 (unconstrained)
• MANE Select transcript: NM_001317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2440
Approved symbol	CSH1
Name	chorionic somatomammotropin hormone 1
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	hCS-A, CSA, PL, CSMT, FLJ75407
Ensembl gene	ENSG00000136488
Ensembl biotype	protein_coding
OMIM	150200
Entrez	1442

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 34 protein_coding, 7 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000316193

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 5: 2

ENST00000316193, ENST00000329882, ENST00000453363, ENST00000558284, ENST00000558661, ENST00000610991, ENST00001104037, ENST00001104038, ENST00001104039, ENST00001104040, ENST00001104041, ENST00001104042, ENST00001104043, ENST00001104044, ENST00001104045, ENST00001104046, ENST00001104047, ENST00001104048, ENST00001104049, ENST00001104050, ENST00001104051, ENST00001104052, ENST00001104053, ENST00001104054, ENST00001104055, ENST00001104056, ENST00001104057, ENST00001104058, ENST00001104059, ENST00001104060, ENST00001104061, ENST00001104062, ENST00001125917, ENST00001125918, ENST00001125919, ENST00001125920, ENST00001125921, ENST00001125922, ENST00001125923, ENST00001125924, ENST00001125925, ENST00001125926, ENST00001142758

RefSeq mRNA: 1 — MANE Select: NM_001317 NM_001317

CCDS: CCDS11649

Canonical transcript exons

ENST00000316193 — 5 exons

Exon	Start	End
ENSE00002449213	63895731	63895850
ENSE00002468625	63895473	63895637
ENSE00002504378	63896502	63896574
ENSE00002522073	63896075	63896235
ENSE00002559899	63894918	63895219

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 99.88.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3750 / max 284.7748, expressed in 6 samples.

Highest expression (Bgee): placenta, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis, pituitary gland, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CSH1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pituitary	eqtl	1.3e-03	+0.48	17:63918839:T:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
167508	0.1795	6
167507	0.1081	4
208315	0.0485	3
167506	0.0362	3
208314	0.0027	2

Top tissues by expression

showing 100 of 105 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	99.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.50	gold quality
adenohypophysis	UBERON:0002196	83.77	gold quality
pituitary gland	UBERON:0000007	83.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.60	gold quality
smooth muscle tissue	UBERON:0001135	67.29	gold quality
monocyte	CL:0000576	53.39	gold quality
leukocyte	CL:0000738	51.58	gold quality
duodenum	UBERON:0002114	49.62	gold quality
muscle tissue	UBERON:0002385	43.94	gold quality
colonic epithelium	UBERON:0000397	41.35	gold quality
cortical plate	UBERON:0005343	40.26	gold quality
sural nerve	UBERON:0015488	38.97	gold quality
adrenal tissue	UBERON:0018303	38.81	gold quality
tonsil	UBERON:0002372	38.63	gold quality
bone marrow cell	CL:0002092	38.27	gold quality
lower esophagus mucosa	UBERON:0035834	37.87	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
granulocyte	CL:0000094	35.53	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	32.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
vermiform appendix	UBERON:0001154	30.93	gold quality
urinary bladder	UBERON:0001255	30.77	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
blood	UBERON:0000178	29.44	silver quality
brain	UBERON:0000955	28.51	gold quality
myometrium	UBERON:0001296	28.44	gold quality
cerebellum	UBERON:0002037	28.40	gold quality
spleen	UBERON:0002106	28.27	gold quality
cerebellar cortex	UBERON:0002129	28.09	gold quality
cerebellar hemisphere	UBERON:0002245	28.06	gold quality
primary visual cortex	UBERON:0002436	27.47	gold quality
right coronary artery	UBERON:0001625	27.42	gold quality
fallopian tube	UBERON:0003889	27.17	gold quality
islet of Langerhans	UBERON:0000006	27.06	gold quality
endometrium	UBERON:0001295	27.05	gold quality
pancreas	UBERON:0001264	27.00	gold quality
stomach	UBERON:0000945	26.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	26.63	gold quality
testis	UBERON:0000473	26.46	gold quality
right testis	UBERON:0004534	26.44	silver quality
left testis	UBERON:0004533	26.40	silver quality
gall bladder	UBERON:0002110	25.98	gold quality
left coronary artery	UBERON:0001626	25.97	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
multicellular organism	UBERON:0000468	25.56	gold quality
heart	UBERON:0000948	25.09	gold quality
lung	UBERON:0002048	25.00	gold quality
ovary	UBERON:0000992	24.89	gold quality
body of stomach	UBERON:0001161	24.87	silver quality
heart left ventricle	UBERON:0002084	24.53	gold quality
fundus of stomach	UBERON:0001160	24.33	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
tibial artery	UBERON:0007610	23.85	gold quality
right frontal lobe	UBERON:0002810	23.84	gold quality
popliteal artery	UBERON:0002250	23.82	gold quality
intestine	UBERON:0000160	23.78	gold quality
rectum	UBERON:0001052	23.51	gold quality
colon	UBERON:0001155	23.33	gold quality
right ovary	UBERON:0002118	23.25	gold quality
calcaneal tendon	UBERON:0003701	23.08	gold quality
small intestine	UBERON:0002108	23.03	gold quality
temporal lobe	UBERON:0001871	22.91	gold quality
saliva-secreting gland	UBERON:0001044	22.69	gold quality
subcutaneous adipose tissue	UBERON:0002190	22.69	gold quality
body of uterus	UBERON:0009853	22.67	gold quality
putamen	UBERON:0001874	22.44	gold quality
ascending aorta	UBERON:0001496	22.39	gold quality
adipose tissue	UBERON:0001013	22.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	22.35	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	22.34	gold quality
thoracic aorta	UBERON:0001515	22.29	gold quality
right adrenal gland cortex	UBERON:0035827	22.27	gold quality
thoracic mammary gland	UBERON:0005200	22.21	gold quality
cortex of kidney	UBERON:0001225	21.85	gold quality
omental fat pad	UBERON:0010414	21.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	21.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	21.58	gold quality
skin of leg	UBERON:0001511	21.45	gold quality
left ovary	UBERON:0002119	21.45	gold quality
descending thoracic aorta	UBERON:0002345	21.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	21.37	gold quality
thyroid gland	UBERON:0002046	21.26	silver quality
anterior cingulate cortex	UBERON:0009835	21.26	gold quality
vagina	UBERON:0000996	21.25	gold quality
prostate gland	UBERON:0002367	21.23	gold quality
nucleus accumbens	UBERON:0001882	21.19	gold quality
left lobe of thyroid gland	UBERON:0001120	21.15	silver quality
left uterine tube	UBERON:0001303	20.89	gold quality
substantia nigra	UBERON:0002038	20.38	gold quality
apex of heart	UBERON:0002098	20.28	gold quality
hypothalamus	UBERON:0001898	19.98	gold quality
mucosa of transverse colon	UBERON:0004991	19.91	gold quality
upper lobe of left lung	UBERON:0008952	19.57	gold quality
minor salivary gland	UBERON:0001830	19.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	19.34	gold quality
right lobe of thyroid gland	UBERON:0001119	19.19	gold quality
caudate nucleus	UBERON:0001873	19.10	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	21675.28
E-MTAB-6678	yes	15358.56
E-MTAB-6701	yes	11059.05
E-ANND-3	no	0.82

HPA expression

RNA tissue specificity: Tissue enriched

16 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	9234.3	high
Smooth muscle	tissue	37.0	not detected
Spleen	tissue	24.6	not detected
Stomach 1	tissue	18.8	not detected
Lung	tissue	10.1	not detected
Endometrium 1	tissue	6.2	not detected
Pancreas	tissue	3.7	not detected
Salivary gland	tissue	1.0	not detected
Tonsil	tissue	1.0	not detected
Heart muscle	tissue	0.9	not detected
Thymus	tissue	0.7
Pituitary gland	tissue	0.5	low
Colon	tissue	0.5	not detected
Duodenum	tissue	0.4	not detected
Ovary	tissue	0.2	not detected
Small intestine	tissue	0.1	not detected

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, FOXM1, HAND1, ID2, NFIC, NR3C1, PITX2, POU1F1, RFX1, SP1, TFAP2A

miRNA regulators (miRDB)

Targeting CSH1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

6 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Functional genomics

gnomAD constraint: pLI 0.00911, LOEUF 1.21, missense Z 0.0684 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000316193 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈16% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:63,895,025–63,896,085	175 / 187.2	0.93	no
17:63,896,086–63,896,203	4 / 39.0	0.10	yes (p 2.1e-08)
17:63,896,204–63,896,511	11 / 17.0	0.65	no

Literature-anchored findings (GeneRIF, showing 22)

• Investigation of the GRB2, GRB7, and CSH1 genes as candidates for the Silver-Russell syndrome (SRS) on chromosome 17q. (PMID:11897833)
• a role for CSH1 haploinsufficiency in the etiology of growth retardation (PMID:14642004)
• These data implicate ETS-domain family members in the regulation of the CS locus in placenta and pituitary cells. (PMID:14673137)
• We showed that intra-arterial infusion of human placental lactogen primarily decreased coronary, renal & iliac blood flow. Mechanism of this response was shown to be due to inhibition of vasodilatory beta2-adrenergic receptor-mediated effect. (PMID:16410683)
• crystal structure of the free state of human PL has been determined to 2.0 A resolution showing the molecule possesses an overall structure similar to other long chain four-helix bundle cytokines (PMID:16546209)
• The present findings indicate that the concentration of human placental lactogen (hPL) and human chorionic gonadotropin (beta hCG) mRNA is significantly higher in the cellular component of maternal blood samples than in the plasma component. (PMID:16950818)
• A CSH1 deletion carrier with nearly complete hypomethylation at the ICR1 locus had the characteristic clinical signs of Silver Russel syndrome, ruling out a causal relationship. (PMID:17400796)
• Placental lactogen is a novel ligand of stabilin-1. (PMID:18292525)
• Three single nucleotide polymorphisms in CGB5 and CSH1 genes were genotyped for 844 offspring of the cases and controls. Maternal breast cancer risk did not significantly differ by the offspring’s carrier status of the three SNPs. (PMID:19047151)
• maternal smoking associated with a reduction in cord blood hPL (PMID:19290844)
• The human growth hormone/chorionic somatomammotropin at chromosome 17 is implicated in regulation of postnatal and intrauterine growth. (PMID:20233782)
• Results strongly support a conformationally mediated obligate-ordered prolactin receptor binding for each of the three lactogenic hormones: prolactin, growth hormone, and placental lactogen. (PMID:20427283)
• Data conclude that members of the C/EBP and Ets families can differentially modulate CS-Benh and CS-Aenh activity. (PMID:21737519)
• hPL-A is involved in the regulation of pancreatic beta cells activity. (PMID:21765243)
• results are consistent with a pleiotropic effect of placental hGH/CSH genes at the maternal-fetal interface relating to the regulation of fetal growth and the risk of affected maternal metabolism. (PMID:22387044)
• altered expression of placenta lactogen appears not to be causal for betamethasone-induced fetal growth restriction in the human (PMID:23465880)
• Expression of placental lactogen mRNA is increased in plasma of women with placenta previa and invasive placenta. (PMID:23744883)
• These results indicate that placental lactogen induces CYP2E1 expression via PI3-kinase pathway in human hepatocytes. (PMID:24408518)
• Placental lactogen is expressed but is not translated into protein in breast cancer. (PMID:24475273)
• FGF-2b and hPL-A are promising candidates for regenerative therapy in Diabetes Mellitus by inducing de-differentiation of stem cells modulating pivotal endocrine genes. (PMID:29068419)
• Obesity and regulation of human placental lactogen production in pregnancy. (PMID:32500948)
• Plasmin generates vasoinhibin-like peptides by cleaving prolactin and placental lactogen. (PMID:34601001)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gh1	ENSDARG00000038185
mus_musculus	Gh	ENSMUSG00000020713
rattus_norvegicus	Gh1	ENSRNOG00000011207

Paralogs (5): GH2 (ENSG00000136487), PRL (ENSG00000172179), CSHL1 (ENSG00000204414), CSH2 (ENSG00000213218), GH1 (ENSG00000259384)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95707) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 40 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased brown adipose tissue amount	1
increased white adipose tissue amount	1
decreased bone mineral density	1
abnormal heart morphology	1
small liver	1
abnormal spleen morphology	1
small spleen	1
decreased body length	1
decreased body weight	1
decreased locomotor activity	1
reduced fertility	1
reduced female fertility	1
male infertility	1
female infertility	1
delayed sexual maturation	1
abnormal kidney morphology	1
small heart	1
disproportionate dwarf	1
delayed vaginal opening	1
decreased heart weight	1
small kidney	1
thrombocytopenia	1
abnormal bone structure	1
decreased kidney weight	1
decreased lean body mass	1

+15 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Vicugna pacos	P37885	100.0%	Diamond
Ovis aries	P67930	100.0%	Diamond
Capra hircus	P67931	100.0%	Diamond
Camelus dromedarius	Q7YRR6	100.0%	Diamond
Bos taurus	P01246	99.5%	Diamond
Pan troglodytes	P58756	99.5%	Diamond
Balaenoptera physalus	Q659Q8	99.5%	Diamond
Hippopotamus amphibius	Q7YQB8	99.5%	Diamond
Bos grunniens	Q864S7	99.5%	Diamond
Delphinus delphis	Q8MI73	99.5%	Diamond
Bubalus bubalis	O18938	99.1%	Diamond
Cervus elaphus	P56437	99.1%	Diamond
Bos frontalis	Q1HFN3	99.1%	Diamond
Giraffa camelopardalis	Q7YQD2	99.1%	Diamond
Sus scrofa	P01248	98.9%	Diamond
Vulpes vulpes	P10766	98.9%	Diamond
Loxodonta africana	P20392	98.9%	Diamond
Canis lupus familiaris	P33711	98.9%	Diamond
Felis catus	P46404	98.6%	Diamond
Galago senegalensis	Q9GKA1	98.6%	Diamond
Xanthonycticebus pygmaeus	Q9GMB2	98.6%	Diamond
Acipenser gueldenstaedtii	P26773	98.4%	Diamond
Ailuropoda melanoleuca	Q8HYE5	97.9%	Diamond
Equus caballus	P01245	97.4%	Diamond
Neogale vison	P19795	97.4%	Diamond
Gallus gallus	P08998	96.8%	Diamond
Meleagris gallopavo	P22077	96.8%	Diamond
Trichosurus vulpecula	O62754	96.7%	Diamond
Monodelphis domestica	Q9GL60	96.7%	Diamond
Nannospalax ehrenbergi	O70615	96.3%	Diamond
Macaca mulatta	P33093	96.3%	Diamond
Mesocricetus auratus	P37886	96.3%	Diamond
Oryctolagus cuniculus	P46407	95.8%	Diamond
Anas platyrhynchos	P11228	95.4%	Diamond
Saimiri boliviensis boliviensis	P58343	94.5%	Diamond
Callithrix jacchus	Q9GMB3	94.5%	Diamond
Struthio camelus	Q9PWG3	94.0%	Diamond
Cavia porcellus	Q9JKM4	93.2%	Diamond
Balaenoptera borealis	P33092	91.6%	Diamond
Chelonia mydas	P34005	91.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CSHL1	protein-coding	1444
GH1	protein-coding	2688
PRR29-AS1	ncRNA	400612
SCN4A	protein-coding	6329
PRR29	protein-coding	92340
CD79B	protein-coding	974
CSH2	protein-coding	1443
GH2	protein-coding	2689
SMARCD2	protein-coding	6603

Protein

Protein identifiers

Chorionic somatomammotropin hormone 1 — P0DML2 (reviewed: P0DML2)

Alternative names: Lactogen, Placental lactogen

All UniProt accessions (5): A0A087WUG6, A6NFB4, A8K6C2, B1A4H2, P0DML2

UniProt curated annotations — full annotation on UniProt →

Function. Produced only during pregnancy and is involved in stimulating lactation, fetal growth and metabolism. Does not interact with GHR but only activates PRLR through zinc-induced dimerization.

Subunit / interactions. Can be found in a monomeric as well as dimeric form.

Subcellular location. Secreted.

Miscellaneous. CSH1 sequence only differs from CSH2 sequence in 1 aa.

Similarity. Belongs to the somatotropin/prolactin family.

RefSeq proteins (1): NP_001308* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001400	Somatotropin/Prolactin	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR018116	Somatotropin_CS	Conserved_site
IPR034975	Somatotropin	Family

Pfam: PF00103

UniProt features (25 total): helix 9, sequence conflict 4, disulfide bond 4, turn 3, binding site 2, signal peptide 1, chain 1, strand 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
1Z7C	Crystal Structure of Human Placental Lactogen	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DML2-F1	82.67	0.49

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Position	Role
44	Zn(2+)
200	Zn(2+)

Disulfide bonds (4)

Type	Positions
Disulfide bond	79–191
In monomeric form	208–215
Interchain (with c-215)	208
Interchain (with c-208)	215

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-982772	Growth hormone receptor signaling	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-168256	Immune System	—
R-HSA-1170546	Prolactin receptor signaling	electronic

MSigDB gene sets: 75 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_GROWTH_HORMONE, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_HORMONE, GNF2_KISS1

GO Biological Process (5): response to nutrient levels (GO:0031667), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), animal organ development (GO:0048513), growth hormone receptor signaling pathway (GO:0060396), signal transduction (GO:0007165)

GO Molecular Function (5): growth hormone receptor binding (GO:0005131), hormone activity (GO:0005179), growth factor activity (GO:0008083), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), endosome lumen (GO:0031904), vesicle (GO:0031982), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Cytokine Signaling in Immune system	2
Immune System	1

GO top-level categories

27 GO namespaces:

Category	Terms
cellular anatomical structure	3
receptor ligand activity	2
response to stimulus	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
animal gross anatomical part developmental process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to growth hormone stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine receptor binding	1
hormone receptor binding	1
cation binding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endosome	1
intracellular organelle lumen	1
membrane-bounded organelle	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
endoplasmic reticulum	CC	direct assay
vesicle	CC	direct assay

Protein interactions and networks

IntAct

Human interaction partners of CSH1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
PSMD9	direct interaction	0.610	5
SGTB	physical association	0.560	3
GH1	association	0.350	2
H6PD	association	0.350	1

BioGRID (18 interactions; top human partners by supporting records): CSH2 (Affinity Capture-MS; 2 records), GH1 (Affinity Capture-MS; 2 records), ISCA1 (Affinity Capture-MS; 2 records), PSMD9 (Reconstituted Complex; 2 records), CINP (Affinity Capture-MS), CSHL1 (Affinity Capture-MS), H6PD (Affinity Capture-MS), KLHL8 (Affinity Capture-MS), PADI2 (Affinity Capture-MS), PTPN12 (Two-hybrid), SGTB (Two-hybrid), SMAD2 (Two-hybrid), SMAD4 (Two-hybrid), SMAD9 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for CSH1: 38 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	8
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 293):

Position(s)	Effect	Δscore	Sites
17:63895220–63895221	acceptor_loss	1.0000	6
17:63895227	acceptor_gain	1.0000
17:63895496	donor_gain	1.0000
17:63895729–63895730	donor_loss	1.0000	4
17:63895224	acceptor_gain	0.9900
17:63895495	donor_gain	0.9900
17:63895638–63895639	acceptor_loss	0.9900	6
17:63895726	donor_loss	0.9900
17:63896073–63896074	donor_loss	0.9900	4
17:63896500–63896501	donor_loss	0.9900	5

AlphaMissense

196 missense substitutions predicted likely pathogenic (of 1,430 scored), across 68 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D195	8	0.868	0.921
W112	7	0.873	0.933
F192	7	0.861	0.937
F202	7	0.851	0.959
F57	7	0.829	0.941
C208	7	0.811	0.903
C191	7	0.780	0.839
C79	7	0.772	0.831
C215	7	0.770	0.840
M196	5	0.764	0.819
P115	5	0.737	0.820
F36	5	0.720	0.757
F172	4	0.857	0.910
L102	4	0.819	0.894
F217	4	0.819	0.885
A50	4	0.747	0.914
F80	3	0.850	0.850
S105	3	0.836	0.903
L101	3	0.823	0.919
L203	3	0.806	0.893

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Testicular Germ Cell Tumor)

Disease associations

OMIM: gene MIM:150200 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST008839_508	Height	5e-22
GCST001956_11	Height	3e-14
GCST002702_29	Height	2e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Colforsin	decreases expression, increases reaction, affects cotreatment	2
Valproic Acid	decreases expression, increases reaction, affects cotreatment, increases methylation	2
propionaldehyde	decreases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
afimoxifene	decreases expression, decreases reaction	1
cobaltous chloride	increases reaction, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
Arsenic Trioxide	decreases expression	1
Ethanol	decreases expression	1
Fonofos	increases methylation	1
Estrogens	decreases expression, decreases reaction	1
Hydrogen Peroxide	affects expression	1
Parathion	increases methylation	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.