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
• Cancer dependency (DepMap): dependent in 39.9% of screened cell lines
• 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: 7 — 5 protein_coding, 2 retained_intron

ENST00000336844, ENST00000345366, ENST00000392886, ENST00000558516, ENST00000559928, ENST00000560142, ENST00000613718

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167501	0.0350	5

Top tissues by expression

236 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, TEAD1

miRNA regulators (miRDB)

4 targeting CSH2, 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-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

DepMap (CRISPR cell-line fitness): dependent in 39.9% of screened cell lines.

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)

Protein

Protein identifiers

Chorionic somatomammotropin hormone 2 — P0DML3 (reviewed: P0DML3)

Alternative names: Lactogen, Placental lactogen

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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 44; 200

Disulfide bonds (4): 79–191, 208–215, 208, 215

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

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 (6): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), vesicle (GO:0031982), extracellular region (GO:0005576), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

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
anatomical structure development	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

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CSH2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
CSH2	SGTB	psi-mi:“MI:0915”(physical association)	0.560
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530
SCG5	CSH2	psi-mi:“MI:0915”(physical association)	0.400
CSH1	GH1	psi-mi:“MI:0914”(association)	0.350
CSH2	GH1	psi-mi:“MI:0914”(association)	0.350
CSH2	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
CSH2	SGTB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): CSH1 (Reconstituted Complex), CSH1 (Protein-peptide), CSH2 (Affinity Capture-MS), GH1 (Affinity Capture-MS), CSH2 (Affinity Capture-MS), CSH2 (Affinity Capture-MS), CSH2 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), CSH2 (Two-hybrid), SGTB (Two-hybrid), CSH2 (Two-hybrid), CINP (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), CSH2 (Affinity Capture-MS), CSH2 (Affinity Capture-MS)

ESM2 similar proteins: A0S0B0, A3FBE9, B6CKP4, O73848, P01241, P01244, P05231, P06880, P08505, P08998, P09321, P09586, P09611, P0DML2, P0DML3, P11228, P14188, P16038, P19795, P20294, P20607, P22077, P26441, P37886, P41683, P43431, P46650, P51494, P51642, P58343, P58756, P58757, P79341, Q07370, Q0GGL7, Q14406, Q25BC2, Q28819, Q2XNF5, Q5I6E3

Diamond homologs: O12980, O13188, O18938, O62754, O70615, O73848, O73849, O93359, O93360, P01241, P01242, P01244, P01245, P01246, P01248, P06880, P07064, P08591, P08899, P08998, P09113, P09538, P0DML2, P0DML3, P10298, P10607, P10766, P10813, P10814, P11228, P12855, P12856, P19795, P20332, P20391, P20392, P22077, P26773, P26774, P29971

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

553 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63872319:AGCCT:A	acceptor_gain	1.0000
17:63872322:CT:C	acceptor_gain	1.0000
17:63872575:ACCC:A	donor_gain	1.0000
17:63872576:CCCC:C	donor_gain	1.0000
17:63872600:C:A	donor_gain	1.0000
17:63872605:AGGT:A	donor_gain	1.0000
17:63872608:T:TA	donor_gain	1.0000
17:63872670:ACT:A	donor_gain	1.0000
17:63872671:CTC:C	donor_gain	1.0000
17:63872740:TT:T	acceptor_gain	1.0000
17:63872831:TCA:T	donor_loss	1.0000
17:63872832:CA:C	donor_loss	1.0000
17:63872833:A:AC	donor_gain	1.0000
17:63872834:C:CC	donor_gain	1.0000
17:63872834:CGG:C	donor_gain	1.0000
17:63873177:A:AC	donor_gain	1.0000
17:63873178:C:CC	donor_gain	1.0000
17:63873178:CAA:C	donor_gain	1.0000
17:63873178:CAAA:C	donor_gain	1.0000
17:63872320:GCCT:G	acceptor_gain	0.9900
17:63872321:CCTC:C	acceptor_gain	0.9900
17:63872323:TC:T	acceptor_loss	0.9900
17:63872324:C:CA	acceptor_loss	0.9900
17:63872324:C:CC	acceptor_gain	0.9900
17:63872325:T:G	acceptor_loss	0.9900
17:63872327:C:CT	acceptor_gain	0.9900
17:63872331:G:C	acceptor_gain	0.9900
17:63872331:G:GC	acceptor_gain	0.9900
17:63872575:AC:A	donor_gain	0.9900
17:63872575:ACC:A	donor_gain	0.9900

AlphaMissense

1429 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63872174:G:C	F202L	0.960
17:63872174:G:T	F202L	0.960
17:63872176:A:G	F202L	0.960
17:63873179:A:C	F57L	0.944
17:63873179:A:T	F57L	0.944
17:63873181:A:G	F57L	0.944
17:63872697:C:A	W112C	0.927
17:63872697:C:G	W112C	0.927
17:63872204:G:C	F192L	0.926
17:63872204:G:T	F192L	0.926
17:63872206:A:G	F192L	0.926
17:63872205:A:G	F192S	0.913
17:63872699:A:G	W112R	0.908
17:63872699:A:T	W112R	0.908
17:63872731:A:G	L101P	0.903
17:63872157:C:G	C208S	0.898
17:63872158:A:T	C208S	0.898
17:63872264:A:C	F172L	0.895
17:63872264:A:T	F172L	0.895
17:63872266:A:G	F172L	0.895
17:63873180:A:C	F57C	0.894
17:63873201:G:T	A50D	0.894
17:63872196:T:G	D195A	0.886
17:63872719:G:A	S105F	0.886
17:63872195:G:C	D195E	0.884
17:63872195:G:T	D195E	0.884
17:63872172:A:G	L203P	0.881
17:63872197:C:G	D195H	0.880
17:63872129:G:C	F217L	0.873
17:63872129:G:T	F217L	0.873

dbSNP variants (sampled 300 via entrez): RS1000434208 (17:63873422 TTC>T), RS1003241292 (17:63874955 C>T), RS1004246923 (17:63873683 G>A), RS1004299147 (17:63874024 G>A,C), RS1005243826 (17:63872426 G>T), RS1008326744 (17:63874597 G>A), RS1009200143 (17:63872983 A>G), RS1009334439 (17:63873394 C>G,T), RS1010279262 (17:63871907 G>A), RS1012596215 (17:63874929 G>A), RS1015671661 (17:63873703 T>C), RS1015722679 (17:63874103 T>G), RS1016672760 (17:63872439 C>T), RS1017773870 (17:63871670 A>C), RS1018577265 (17:63875307 A>G)

Disease associations

OMIM: gene MIM:118820 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002647_154	Height	1.000000e-42
GCST008839_218	Height	4.000000e-46
GCST90011898_51	Alanine aminotransferase levels	5.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

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	affects cotreatment, decreases expression	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)

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