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CSHL1

gene
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Also known as hCS-LCSLCS-5MGC149868

Summary

CSHL1 (chorionic somatomammotropin hormone like 1, HGNC:2442) is a protein-coding gene on chromosome 17q23.3, encoding Chorionic somatomammotropin hormone-like 1 (Q14406). May be a novel gestational hormone required to compensate for absence of other members of the GH/CS cluster during gestation.

The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed 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. This particular family member is expressed in placental villi, although it was originally thought to be a pseudogene. In fact, alternative splicing suggests that the majority of the transcripts would be unable to express a secreted protein. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 1444 — RefSeq curated summary.

At a glance

  • GWAS associations: 5
  • Clinical variants (ClinVar): 62 total
  • MANE Select transcript: NM_022579

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:2442
Approved symbolCSHL1
Namechorionic somatomammotropin hormone like 1
Location17q23.3
Locus typegene with protein product
StatusApproved
AliaseshCS-L, CSL, CS-5, MGC149868
Ensembl geneENSG00000204414
Ensembl biotypeprotein_coding
OMIM603515
Entrez1444

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000259003, ENST00000309894, ENST00000346606, ENST00000438387, ENST00000450719, ENST00000558099, ENST00000558609, ENST00000560999, ENST00000561003

RefSeq mRNA: 7 — MANE Select: NM_022579 NM_001318, NM_001321067, NM_001321068, NM_001321069, NM_022579, NM_022580, NM_022581

CCDS: CCDS11652, CCDS42370, CCDS45759, CCDS82189

Canonical transcript exons

ENST00000309894 — 5 exons

ExonStartEnd
ENSE000009253196391074563910924
ENSE000022954036391042063910535
ENSE000024503446391016263910326
ENSE000027038966391118763911258
ENSE000027162236390960863909908

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 94.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1655 / max 1333.5719, expressed in 13 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
16752911.101211
1675101.165513

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
placentaUBERON:000198794.74gold quality
adenohypophysisUBERON:000219684.52gold quality
pituitary glandUBERON:000000783.84gold quality
vastus lateralisUBERON:000137974.08gold quality
thymusUBERON:000237073.95gold quality
quadriceps femorisUBERON:000137773.17gold quality
epithelium of bronchusUBERON:000203171.02gold quality
tracheaUBERON:000312670.09gold quality
dorsal plus ventral thalamusUBERON:000189769.29gold quality
dorsal root ganglionUBERON:000004469.11gold quality
frontal poleUBERON:000279559.18gold quality
endometrium epitheliumUBERON:000481159.15gold quality
middle frontal gyrusUBERON:000270258.97gold quality
paraflocculusUBERON:000535158.78gold quality
layer of synovial tissueUBERON:000761657.91gold quality
cerebellar vermisUBERON:000472057.59gold quality
metanephric glomerulusUBERON:000473655.97gold quality
Brodmann (1909) area 10UBERON:001354150.75gold quality
smooth muscle tissueUBERON:000113545.98gold quality
colonic epitheliumUBERON:000039737.20gold quality
muscle tissueUBERON:000238537.03gold quality
lower esophagus mucosaUBERON:003583436.73gold quality
ventricular zoneUBERON:000305336.48gold quality
cortical plateUBERON:000534336.47gold quality
bone marrow cellCL:000209236.16gold quality
ganglionic eminenceUBERON:000402335.49gold quality
skeletal muscle tissueUBERON:000113434.76gold quality
bone marrowUBERON:000237134.10gold quality
monocyteCL:000057634.02silver quality
leukocyteCL:000073833.90silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no0.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, GLI3, NR1I2

miRNA regulators (miRDB)

6 targeting CSHL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-477599.9875.006394
HSA-MIR-590-3P99.9674.346478
HSA-MIR-4477A98.8369.752952
HSA-MIR-391896.1364.651300
HSA-MIR-541-3P96.0766.111271
HSA-MIR-654-5P96.0766.181280

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriogh1ENSDARG00000038185
mus_musculusGhENSMUSG00000020713
rattus_norvegicusGh1ENSRNOG00000011207

Paralogs (5): GH2 (ENSG00000136487), CSH1 (ENSG00000136488), PRL (ENSG00000172179), CSH2 (ENSG00000213218), GH1 (ENSG00000259384)

Protein

Protein identifiers

Chorionic somatomammotropin hormone-like 1 — Q14406 (reviewed: Q14406)

Alternative names: Lactogen-like

All UniProt accessions (5): Q14406, A0A0B4J1R0, H0YKQ4, H7C3R7, I6L999

UniProt curated annotations — full annotation on UniProt →

Function. May be a novel gestational hormone required to compensate for absence of other members of the GH/CS cluster during gestation.

Subcellular location. Secreted.

Similarity. Belongs to the somatotropin/prolactin family.

Isoforms (4)

UniProt IDNamesCanonical?
Q14406-11yes
Q14406-22
Q14406-33
Q14406-44

RefSeq proteins (7): NP_001307996, NP_001307997, NP_001307998, NP_001309, NP_072101, NP_072102, NP_072103 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001400Somatotropin/ProlactinFamily
IPR0090794_helix_cytokine-like_coreHomologous_superfamily
IPR018116Somatotropin_CSConserved_site
IPR034975SomatotropinFamily

Pfam: PF00103

UniProt features (9 total): splice variant 3, binding site 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q14406-F175.990.28

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; 205

Disulfide bonds (1): 213–220

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_GROWTH_HORMONE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_HORMONE, GOMF_SIGNALING_RECEPTOR_BINDING, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_CELL_SURFACE_RECEPTOR_PROTEIN_TYROSINE_KINASE_SIGNALING_PATHWAY, GOMF_HORMONE_RECEPTOR_BINDING, GOMF_HORMONE_ACTIVITY, GOBP_REGULATION_OF_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT

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

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
receptor ligand activity2
response to stimulus1
cell surface receptor signaling pathway via JAK-STAT1
regulation of receptor signaling pathway via JAK-STAT1
positive regulation of receptor signaling pathway via STAT1
anatomical structure development1
cell surface receptor protein tyrosine kinase signaling pathway1
cellular response to growth hormone stimulus1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
cytokine receptor binding1
hormone receptor binding1
cation binding1
binding1
intracellular anatomical structure1
vacuole1
plasma membrane1
membrane-bounded organelle1

Protein interactions and networks

STRING

424 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CSHL1NKAPQ8N5F7765
CSHL1DTX1Q86Y01490
CSHL1GAB2Q9UQC2475
CSHL1TEAD3Q99594426
CSHL1C4orf36Q96KX1400
CSHL1OR8H1Q8NGG4379
CSHL1CSH1P01243372
CSHL1CSH1P01243368
CSHL1OR6N1Q8NGY5348
CSHL1KCNIP3Q9Y2W7320
CSHL1GHRP10912316
CSHL1PSG9Q00887314
CSHL1OR13F1Q8NGS4314
CSHL1OR10A5Q9H207313
CSHL1OR10G7Q8NGN6312

IntAct

10 interactions, top by confidence:

ABTypeScore
CFTRCSHL1psi-mi:“MI:0915”(physical association)0.370
Prdm16ESYT2psi-mi:“MI:0914”(association)0.350
MecomESYT2psi-mi:“MI:0914”(association)0.350
CSH2GH1psi-mi:“MI:0914”(association)0.350
CSH1H6PDpsi-mi:“MI:0914”(association)0.350

BioGRID (7): UBR4 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), CSHL1 (Affinity Capture-MS), CSHL1 (Affinity Capture-MS), CSHL1 (Affinity Capture-MS), CSHL1 (Affinity Capture-MS), CSHL1 (PCA)

ESM2 similar proteins: A0A2R8QHQ6, A0A3Q1LRJ2, A0A8M9PDM1, B4ER10, B5DFM7, B6ZK77, B8JI67, E1B9E5, E9Q8Q8, E9Q9F6, O35256, O35257, P01241, P01242, P05402, P06880, P08998, P09321, P09586, P09611, P0DJF3, P0DP43, P11228, P18121, P22077, P37886, P58343, P58757, Q0VCB1, Q14406, Q14956, Q5SY80, Q6AXW8, Q6AY06, Q6NXM3, Q6P7C7, Q6P7N7, Q6PVW7, Q6X782, Q6X784

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

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance49
Likely benign9
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

472 predictions. Top by Δscore:

VariantEffectΔscore
17:63910160:ACCC:Adonor_gain1.0000
17:63910161:CCCC:Cdonor_gain1.0000
17:63910184:T:TAdonor_gain1.0000
17:63910185:C:Adonor_gain1.0000
17:63910190:AGGT:Adonor_gain1.0000
17:63910193:T:TAdonor_gain1.0000
17:63910415:CTCA:Cdonor_loss1.0000
17:63910416:TCA:Tdonor_loss1.0000
17:63910417:CA:Cdonor_loss1.0000
17:63910418:A:ACdonor_gain1.0000
17:63910418:AC:Adonor_loss1.0000
17:63910419:C:CCdonor_gain1.0000
17:63909905:GCCT:Gacceptor_gain0.9900
17:63909906:CCTC:Cacceptor_gain0.9900
17:63909907:CT:Cacceptor_gain0.9900
17:63909909:C:CCacceptor_gain0.9900
17:63909916:G:Cacceptor_gain0.9900
17:63909916:G:GCacceptor_gain0.9900
17:63910160:ACC:Adonor_gain0.9900
17:63910161:CCC:Cdonor_gain0.9900
17:63910163:C:CAdonor_gain0.9900
17:63910298:A:Tacceptor_gain0.9900
17:63910324:GTT:Gacceptor_gain0.9900
17:63910324:GTTC:Gacceptor_loss0.9900
17:63910325:TT:Tacceptor_gain0.9900
17:63910326:TCT:Tacceptor_loss0.9900
17:63910327:C:CCacceptor_gain0.9900
17:63910327:CTG:Cacceptor_loss0.9900
17:63910328:T:Cacceptor_loss0.9900
17:63910412:CCACT:Cdonor_loss0.9900

AlphaMissense

1465 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:63909759:G:CF207L0.835
17:63909759:G:TF207L0.835
17:63909761:A:GF207L0.835
17:63909714:G:CF222L0.825
17:63909714:G:TF222L0.825
17:63909716:A:GF222L0.825
17:63910764:A:CF57L0.796
17:63910764:A:TF57L0.796
17:63910766:A:GF57L0.796
17:63909849:A:CF177L0.774
17:63909849:A:TF177L0.774
17:63909851:A:GF177L0.774
17:63909789:G:CF197L0.772
17:63909789:G:TF197L0.772
17:63909791:A:GF197L0.772
17:63910471:G:CF85L0.720
17:63910471:G:TF85L0.720
17:63910473:A:GF85L0.720
17:63910249:G:CF128L0.666
17:63910249:G:TF128L0.666
17:63910251:A:GF128L0.666
17:63910827:A:CF36L0.639
17:63910827:A:TF36L0.639
17:63910829:A:GF36L0.639
17:63910501:G:CF75L0.595
17:63910501:G:TF75L0.595
17:63910503:A:GF75L0.595
17:63910896:A:CF13L0.585
17:63910896:A:TF13L0.585
17:63910898:A:GF13L0.585

dbSNP variants (sampled 300 via entrez): RS1000195267 (17:63911213 G>A,C), RS1002095340 (17:63912656 A>C), RS1002187387 (17:63909714 G>A), RS1002220260 (17:63909826 T>A,C), RS1002467642 (17:63912530 G>A), RS1003060280 (17:63911868 G>A), RS1003224697 (17:63909180 T>C), RS1003500869 (17:63911970 C>T), RS1004098891 (17:63911357 C>G,T), RS1006037987 (17:63913041 T>C), RS1007123030 (17:63909335 A>T), RS1008478175 (17:63911657 C>T), RS1009065960 (17:63911007 C>G,T), RS1010811551 (17:63912308 G>C), RS1010841221 (17:63912510 T>G)

Disease associations

OMIM: gene MIM:603515 | disease phenotypes: MIM:262400

GenCC curated gene-disease

Mondo (1): isolated growth hormone deficiency type IA (MONDO:0009876)

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

HPO phenotypes

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

GWAS associations

5 associations (top):

StudyTraitp-value
GCST008839_225Height5.000000e-22
GCST010320_31PR interval8.000000e-09
GCST010321_57PR interval6.000000e-09
GCST012227_344Hip circumference adjusted for BMI4.000000e-19
GCST90020028_1584Hip circumference adjusted for BMI3.000000e-24

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0004462PR interval
EFO:0008039BMI-adjusted hip circumference

MeSH disease descriptors (1)

DescriptorNameTree numbers
C537404Pituitary dwarfism 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidincreases expression, increases methylation2
potassium perchlorateincreases expression1
Grape Seed Proanthocyanidinsaffects cotreatment, decreases expression1
Resveratrolaffects cotreatment, decreases expression1
Pioglitazoneincreases expression1
Benzo(a)pyreneaffects methylation1
Catechinaffects cotreatment, decreases expression1
Plant Extractsaffects cotreatment, decreases expression1
Silicon Dioxidedecreases expression1
Zincincreases expression1
Sodium Selenitedecreases expression1
beta-Naphthoflavonedecreases expression1

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot