CSHL1

Chr 17

chorionic somatomammotropin hormone like 1

Also known as: CS-5, CSHP1, CSL, GHB4, hCS-L

NCBI Gene: 1444UniProt: Q14406

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. [provided by RefSeq, Jul 2008]

73
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
-1.7
Missense Z
1.91
LOEUF
0
Active trials
Clinical Summary— CSHL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 51 VUS of 73 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.91LOEUF
pLI 0.000
Z-score -1.30
OE 1.43 (0.94–1.91)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.74Z-score
OE missense 1.43 (1.27–1.62)
181 obs / 126.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.43 (0.94–1.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.43 (1.27–1.62)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.43
0≤1.21.6
LoF obs/exp: 15 / 10.5Missense obs/exp: 181 / 126.1Syn Z: -2.53

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS51
Likely Benign8
Benign3
Conflicting1
10
Pathogenic
51
VUS
8
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
49
2
0
51
Likely Benign
1
7
0
0
8
Benign
0
2
0
1
3
Conflicting
—1
Total15812173

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CSHL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Identification of Unique Genetic Biomarkers of Various Subtypes of Glomerulonephritis Using Machine Learning and Deep Learning
Qing J et al.·Biomolecules
2022
Identification of dysregulated canonical pathways associated with pathogenesis and progression of Amyotrophic Lateral Sclerosis-An integrated bioinformatics approach.
Datta A et al.·Adv Protein Chem Struct Biol
2023
Aflatoxin B1 targeted gene expression profiles in human placental primary trophoblast cells
El-Dairi R et al.·Curr Res Toxicol
2022
HGCA2.0: An RNA-Seq Based Webtool for Gene Coexpression Analysis in Homo sapiens
Zogopoulos VL et al.·Cells
2023
Isolated growth hormone deficiency type IA due to a novel GH1 variant: a case report
Yang X et al.·BMC Med Genomics
2021Case report
Detection of sexually antagonistic transmission distortions in trio datasets
Lucotte EA et al.·Evol Lett
2022
Hypoxia Induced Sex-Difference in Zebrafish Brain Proteome Profile Reveals the Crucial Role of H3K9me3 in Recovery From Acute Hypoxia
Das T et al.·Front Genet
2022Functional
Sex-specific placental transcriptome alterations in late-onset preeclampsia reveal male-biased immune and metabolic dysregulation
Smith MD et al.·Biol Sex Differ
2025
How Placenta Promotes the Successful Reproduction in High-Altitude Populations: A Transcriptome Comparison between Adaptation and Acclimatization
Wu D et al.·Mol Biol Evol
2022
Top 9 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients