CSH2

Summary

CSH2 (chorionic somatomammotropin hormone 2, HGNC:2441) is a protein-coding gene on chromosome 17q23.3, encoding Chorionic somatomammotropin hormone 2 (P0DML3). Produced only during pregnancy and is involved in stimulating lactation, fetal growth and metabolism. It is a selective cancer dependency (DepMap: 39.9% of cell lines).

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. 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, while the ratio of 1 to 2 increases by term. Structural and expression differences provide avenues for developmental regulation and tissue specificity.

Source: NCBI Gene 1443 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 45 total
• Regional missense constraint (gnomAD): 1 of 2 regions constrained (≈42% of expected missense variation)
• GTEx eGene: eQTL in 4 tissues, sQTL in 0 (q < 0.05)
• Cancer dependency (DepMap): dependent in 39.9% of screened cell lines
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.09 (unconstrained)
• MANE Select transcript: NM_020991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2441
Approved symbol	CSH2
Name	chorionic somatomammotropin hormone 2
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	hCS-B, CSB, CS-2
Ensembl gene	ENSG00000213218
Ensembl biotype	protein_coding
OMIM	118820
Entrez	1443

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 19 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000392886

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

ENST00000392886, ENST00000336844, ENST00000345366, ENST00000558516, ENST00000559928, ENST00000560142, ENST00000613718, ENST00001104108, ENST00001104109, ENST00001104110, ENST00001104111, ENST00001104112, ENST00001104113, ENST00001104114, ENST00001104115, ENST00001104116, ENST00001104117, ENST00001104118, ENST00001130444, ENST00001130445, ENST00001130446, ENST00001130447, ENST00001130448, ENST00001130449, ENST00001138769

RefSeq mRNA: 3 — MANE Select: NM_020991 NM_020991, NM_022644, NM_022645

CCDS: CCDS11646, CCDS42368, CCDS42369

Canonical transcript exons

ENST00000392886 — 5 exons

Exon	Start	End
ENSE00002446102	63872577	63872741
ENSE00002464250	63872835	63872954
ENSE00003528601	63873179	63873339
ENSE00003902411	63873605	63873677
ENSE00003903960	63872016	63872323

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 99.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0350 / max 33.0034, expressed in 5 samples.

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

Genetic regulation across tissues (GTEx eQTL / sQTL)

CSH2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	2.3e-55	-0.89	17:63863441:C:T
Brain Cerebellar Hemisphere	eqtl	5.0e-32	-0.90	17:63863358:G:A
Brain Cerebellum	eqtl	2.2e-27	-0.93	17:63847938:C:T
Pituitary	eqtl	4.0e-10	+0.68	17:63918780:A:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
167501	0.0350	5

Top tissues by expression

showing 100 of 236 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	99.23	gold quality
decidua	UBERON:0002450	97.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.99	silver quality
adenohypophysis	UBERON:0002196	67.49	gold quality
pituitary gland	UBERON:0000007	67.21	gold quality
olfactory bulb	UBERON:0002264	65.91	gold quality
type B pancreatic cell	CL:0000169	65.33	gold quality
smooth muscle tissue	UBERON:0001135	64.19	gold quality
vena cava	UBERON:0004087	54.35	gold quality
pancreatic ductal cell	CL:0002079	54.18	silver quality
left testis	UBERON:0004533	53.95	gold quality
right testis	UBERON:0004534	52.88	gold quality
palpebral conjunctiva	UBERON:0001812	52.82	gold quality
epithelial cell of pancreas	CL:0000083	52.54	gold quality
testis	UBERON:0000473	52.26	gold quality
triceps brachii	UBERON:0001509	52.18	gold quality
granulocyte	CL:0000094	51.91	gold quality
upper leg skin	UBERON:0004262	51.41	silver quality
upper arm skin	UBERON:0004263	50.91	gold quality
tibialis anterior	UBERON:0001385	50.64	silver quality
male germ cell	CL:0000015	50.37	gold quality
myocardium	UBERON:0002349	49.92	gold quality
deltoid	UBERON:0001476	49.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
quadriceps femoris	UBERON:0001377	49.18	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
ileal mucosa	UBERON:0000331	49.10	silver quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
sperm	CL:0000019	48.48	gold quality
cervix epithelium	UBERON:0004801	48.41	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
oviduct epithelium	UBERON:0004804	48.19	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
muscle tissue	UBERON:0002385	47.89	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
amniotic fluid	UBERON:0000173	46.79	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
nasal cavity epithelium	UBERON:0005384	45.61	gold quality
mononuclear cell	CL:0000842	45.47	gold quality
monocyte	CL:0000576	45.43	gold quality
leukocyte	CL:0000738	44.95	gold quality
skeletal muscle tissue	UBERON:0001134	44.69	gold quality
squamous epithelium	UBERON:0006914	43.80	gold quality
ventral tegmental area	UBERON:0002691	43.67	gold quality
epithelium of esophagus	UBERON:0001976	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
epithelium of bronchus	UBERON:0002031	43.28	gold quality
bronchus	UBERON:0002185	43.14	gold quality
dorsal plus ventral thalamus	UBERON:0001897	42.78	gold quality
embryo	UBERON:0000922	42.65	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
pharyngeal mucosa	UBERON:0000355	42.55	gold quality
substantia nigra pars reticulata	UBERON:0001966	42.40	gold quality
trachea	UBERON:0003126	42.27	gold quality
cartilage tissue	UBERON:0002418	42.04	gold quality
trigeminal ganglion	UBERON:0001675	42.03	gold quality
pleura	UBERON:0000977	41.59	gold quality
bone marrow cell	CL:0002092	41.46	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
parietal pleura	UBERON:0002400	41.27	gold quality
epithelium of mammary gland	UBERON:0003244	41.25	gold quality
cerebellar hemisphere	UBERON:0002245	41.20	silver quality
mammalian vulva	UBERON:0000997	41.11	gold quality
cerebellum	UBERON:0002037	41.11	silver quality
cerebellar cortex	UBERON:0002129	40.99	silver quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
globus pallidus	UBERON:0001875	40.97	gold quality
esophagus squamous epithelium	UBERON:0006920	40.96	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	40.56	silver quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
tongue	UBERON:0001723	40.09	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
pericardium	UBERON:0002407	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
nipple	UBERON:0002030	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	17.69
E-ANND-3	no	0.49

HPA expression

RNA tissue specificity: Tissue enriched

16 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	3105.6	high
Smooth muscle	tissue	14.1	not detected
Spleen	tissue	8.1	not detected
Stomach 1	tissue	4.9	not detected
Lung	tissue	3.3	not detected
Pituitary gland	tissue	2.2	not detected
Endometrium 1	tissue	2.0	not detected
Pancreas	tissue	1.1	not detected
Thymus	tissue	0.9
Salivary gland	tissue	0.2	not detected
Tonsil	tissue	0.2	not detected
Testis	tissue	0.1	not detected
Cerebral cortex	tissue	0.1	not detected
Colon	tissue	0.1	not detected
Cerebellum	tissue	0.1	not detected
Small intestine	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 3; highest nTPM — Cerebellar cortex (0.1), Precentral gyrus (0.1), Vermis (0.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, TEAD1

miRNA regulators (miRDB)

Targeting CSH2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

4 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-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632

Functional genomics

gnomAD constraint: pLI 0.00948, LOEUF 1.09, missense Z 1.22 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000392886 splits into 2 regions with different missense tolerance; 1 is missense-constrained (≈42% 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
17:63,872,129–63,872,733	145 / 157.8	0.92	no
17:63,872,734–63,873,614	16 / 113.2	0.14	yes (p 6.3e-20)
DepMap (CRISPR cell-line fitness): dependent in 39.9% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): CW9019 (-1.472), SUIT-2 (-1.453), MDA-MB-453 (-1.451), CAS-1 (-1.327), HUP-T3 (-1.276), EFE-184 (-1.252), HCC1954 (-1.228), T3M-4 (-1.209), U-87 MG (-1.195), IMR-32 (-1.14), SF126 (-1.128), HEC-151 (-1.123), H4 (-1.068), SNU-16 (-1.05), NB-1 (-1.048).

Literature-anchored findings (GeneRIF, showing 3)

• Cpn10 and placental lactogen are capable of stimulating the synthesis of type I collagen by human osteoblasts in culture (PMID:12703979)
• Data conclude that members of the C/EBP and Ets families can differentially modulate CS-Benh and CS-Aenh activity. (PMID:21737519)
• 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)

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), CSH1 (ENSG00000136488), PRL (ENSG00000172179), CSHL1 (ENSG00000204414), 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
FTSJ3	protein-coding	117246
PSMC5	protein-coding	5705
SMARCD2	protein-coding	6603
DDX42	protein-coding	11325
CSH1	protein-coding	1442
CSHL1	protein-coding	1444
GH2	protein-coding	2689
GH1	protein-coding	2688

Protein

Protein identifiers

Chorionic somatomammotropin hormone 2 — P0DML3 (reviewed: P0DML3)

Alternative names: Lactogen, Placental lactogen

All UniProt accessions (6): P0DML3, A0A087WUG6, A0A0M6L0F6, A6NIT4, B1A4H9, H0YM39

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

Similarity. Belongs to the somatotropin/prolactin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P0DML3-1	1	yes
P0DML3-2	2
P0DML3-3	3

RefSeq proteins (3): NP_066271, NP_072170, NP_072171 (=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 (15 total): sequence conflict 4, disulfide bond 4, binding site 2, splice variant 2, signal peptide 1, chain 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DML3-F1	83.15	0.52

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

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

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

MSigDB gene sets: 74 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_64, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MODULE_66, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_RESPONSE_TO_GROWTH_HORMONE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_HORMONE, SAKAI_CHRONIC_HEPATITIS_VS_LIVER_CANCER_DN, GOMF_SIGNALING_RECEPTOR_BINDING, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON

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 (5): endoplasmic reticulum (GO:0005783), vesicle (GO:0031982), extracellular region (GO:0005576), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

GO top-level categories

25 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
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 16 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 CSH2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
MEOX2	physical association	0.560	3
SGTB	physical association	0.560	3
SCG5	physical association	0.400	2
GH1	association	0.350	1

BioGRID (34 interactions; top human partners by supporting records): CSH1 (Affinity Capture-MS; 2 records), POLR2A (Affinity Capture-Western; 2 records), SCG5 (Affinity Capture-MS; 2 records), SOST (Affinity Capture-MS; 2 records), CSHL1 (Affinity Capture-MS), GH1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), MEOX2 (Two-hybrid), PTPN12 (Two-hybrid), SGTB (Two-hybrid), SMAD2 (Two-hybrid), SMAD3 (Two-hybrid), SMAD4 (Two-hybrid), SMAD9 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for CSH2: 45 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	8
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 269):

Position(s)	Effect	Δscore	Sites
17:63872324–63872325	acceptor_loss	1.0000	4
17:63872600	donor_gain	1.0000
17:63872833–63872834	donor_loss	1.0000	4
17:63873603–63873604	donor_loss	1.0000	3
17:63872325	acceptor_loss	0.9900	2
17:63872331	acceptor_gain	0.9900
17:63872599	donor_gain	0.9900
17:63872742–63872743	acceptor_loss	0.9900	6
17:63872830	donor_loss	0.9900
17:63873177–63873178	donor_loss	0.9900	5

AlphaMissense

196 missense substitutions predicted likely pathogenic (of 1,429 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	0.816	0.886
W112	7	0.857	0.927
F202	7	0.847	0.960
F192	7	0.843	0.926
F57	7	0.824	0.944
C208	7	0.810	0.898
C191	7	0.762	0.828
C79	7	0.738	0.804
C215	7	0.738	0.812
F36	6	0.736	0.805
M196	5	0.716	0.796
F172	4	0.825	0.895
F217	4	0.805	0.873
L102	4	0.785	0.867
F123	4	0.735	0.792
A50	4	0.730	0.894
P115	4	0.700	0.756
F80	3	0.863	0.863
S105	3	0.818	0.886
L101	3	0.807	0.903

HPA cancer prognostics

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

Disease associations

OMIM: gene MIM:118820 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST008839_501	Height	4e-46
GCST002647_100	Height	1e-42
GCST90011898_137	Alanine aminotransferase levels	5e-9

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
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
aristolochic acid I	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases 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	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fonofos	increases methylation	1
Colforsin	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Cadmium Chloride	increases expression	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

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