MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Alcohol intake frequency | -0.0527 | 0.0121 | 1.35e-05 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: hypertension | 0.0446 | 0.0134 | 8.45e-04 | Wald ratio | 1 | cis | NA |
| Systolic blood pressure automated reading | 0.0234 | 0.00839 | 0.00528 | Wald ratio | 1 | cis | NA |
| Diastolic blood pressure automated reading | 0.0222 | 0.0084 | 0.00815 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone | -0.32 | 0.13 | 0.0141 | Wald ratio | 1 | cis | NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) | 0.062 | 0.0253 | 0.0144 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: depression | 0.0765 | 0.0313 | 0.0147 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: D25 Leiomyoma of uterus | 0.151 | 0.0625 | 0.0157 | Wald ratio | 1 | cis | NA |
| Cancer code self-reported: basal cell carcinoma | 0.174 | 0.0724 | 0.0163 | Wald ratio | 1 | cis | NA |
| Forced expiratory volume in 1-second (FEV1) | -0.0167 | 0.00709 | 0.0187 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: high cholesterol | -0.0547 | 0.0234 | 0.0197 | Wald ratio | 1 | cis | NA |
| Vascular or heart problems diagnosed by doctor: Angina | -0.121 | 0.052 | 0.0202 | Wald ratio | 1 | cis | NA |
| …and 63 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
32 association rows across 28 traits (31 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.
| Trait | best p | lead SNP | n assoc | study | MR status |
|---|---|---|---|---|---|
| MGLL/SHMT1 protein level ratio | 2e-4728 | rs669340 | 1 | GCST90315441 | no MR -> candidate analysis |
| MVK/SHMT1 protein level ratio | 2e-4708 | rs669340 | 1 | GCST90315506 | no MR -> candidate analysis |
| Serine hydroxymethyltransferase, cytosolic levels | 3e-1580 | rs4398149 | 1 | GCST90249535 | no MR -> candidate analysis |
| Serum levels of protein SHMT1 | 1e-63 | rs8067462 | 1 | GCST90086918 | no MR -> candidate analysis |
| Height | 7e-57 | rs669340 | 1 | GCST90245848 | no MR -> candidate analysis |
| Cerebrospinal fluid protein SHMT1 levels | 6e-36 | rs1975822 | 1 | GCST90944573 | no MR -> candidate analysis |
| Blood protein levels | 1e-31 | rs8067462 | 1 | GCST006585 | no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) | 2e-22 | rs4924750 | 1 | GCST90838669 | no MR -> candidate analysis |
| Mitochondrial DNA copy number (adjusted) | 3e-19 | rs7216214 | 1 | GCST90268497 | no MR -> candidate analysis |
| SHMT1 protein levels | 3e-19 | rs140013206 | 2 | GCST90470627 | no MR -> candidate analysis |
| EF-hand calcium-binding domain-containing protein 4B protein | 2e-16 | rs638416 | 1 | GCST90440180 | no MR -> candidate analysis |
| Waist-to-hip ratio adjusted for BMI | 1e-14 | rs7207306 | 2 | GCST009858 | no MR -> candidate analysis |
| …and 16 more traits (see JSON) |
Top diseases by Open Targets association (of 284 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.
| Disease | genetic assoc. | burden (ExWAS) | causal status | MR status |
|---|---|---|---|---|
| multiple sclerosis | 0.217 | — | common-variant locus | no MR -> candidate analysis |
| preeclampsia | 0.46 | — | common-variant locus | no MR -> candidate analysis |
| Hodgkins lymphoma | 0.209 | — | common-variant locus | no MR -> candidate analysis |
| gastrointestinal stromal tumor | 0.182 | — | established (curated) | no MR -> candidate analysis |
| hair color | 0.136 | — | common-variant locus | no MR -> candidate analysis |
Of the 5 rows above, 5 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
| Layer | Result |
|---|---|
| ChEMBL druggability | 0 known modulators (Serine hydroxymethyltransferase, cytosolic) |
| gnomAD constraint | pLI=1.2e-14, LOEUF=1.18 — LoF-tolerant |
| GWAS Catalog | 62 unique SNPs / 124 rows |
| ClinVar | 207 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | 2 clinical annotations across 5 drugs |
phenome — Top 30 of 284 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘SHMT1’ and resolved to ‘Serine hydroxymethyltransferase, cytosolic’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 207 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 28 traits by best p-value, aggregated from 32 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/P34896 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000176974/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL1772927/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SHMT1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SHMT1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SHMT1%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=SHMT1 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/SHMT1 — GWAS Catalog search API (live; release not exposed)