Glycosylphosphatidylinositol biosynthesis defect 16
diseaseOn this page
Also known as GPIBD16mental retardation, autosomal recessive 62
Summary
Glycosylphosphatidylinositol biosynthesis defect 16 (MONDO:0040500) is a disease caused by PIGC (GenCC Strong), with 2 cohort genes.
At a glance
- Causal gene: PIGC (GenCC Strong)
- Cohort genes: 2
- ClinVar variants: 22
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | glycosylphosphatidylinositol biosynthesis defect 16 |
| Mondo ID | MONDO:0040500 |
| OMIM | 617816 |
| DOID | DOID:0081223 |
| UMLS | C4540521 |
| MedGen | 1628197 |
| GARD | 0022577 |
| Is cancer (heuristic) | no |
Also known as: glycosylphosphatidylinositol biosynthesis defect 16 · GPIBD16 · mental retardation, autosomal recessive 62
Data availability: 22 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › glycosylphosphatidylinositol biosynthesis defect 16
Related subtypes (28): cortisone reductase deficiency, familial hyperlipidemia, hypolipoproteinemia, steroid inherited metabolic disorder, corticosterone methyloxidase type 1 deficiency, lipoid proteinosis, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, vitamin D hydroxylation-deficient rickets, type 1B, mitochondrial trifunctional protein deficiency, pancreatic triacylglycerol lipase deficiency, glucocorticoid resistance, syndromic dyslipidemia, inborn disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, disorder of plasmalogens biosynthesis, disorder of phospholipids, sphingolipids and fatty acids biosynthesis, inborn disorder of ketolysis, lysosomal lipid storage disorder, sterol metabolism disorder, disorder of sphingolipid biosynthesis, glycosylphosphatidylinositol biosynthesis defect 18, neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 55, inherited fatty acid metabolism disorder, glycosylphosphatidylinositol biosynthesis defect 15, glycosylphosphatidylinositol biosynthesis defect 17, CYP7B1-related disorder of oxysterol accumulation
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
22 retrieved; paginated sample, class counts are floors:
11 uncertain significance, 4 pathogenic, 2 benign, 2 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1802584 | NM_153747.2(PIGC):c.859G>T (p.Glu287Ter) | C1orf105 | Pathogenic | criteria provided, single submitter |
| 4278926 | NM_153747.2(PIGC):c.794_796delinsT (p.Cys265fs) | C1orf105 | Pathogenic | no assertion criteria provided |
| 4278927 | NM_153747.2(PIGC):c.437_445del (p.Thr146_Thr148del) | C1orf105 | Pathogenic | no assertion criteria provided |
| 4278929 | NM_153747.2(PIGC):c.77A>G (p.Asp26Gly) | C1orf105 | Pathogenic | no assertion criteria provided |
| 917868 | NM_153747.2(PIGC):c.12_13insTTGTGACTAACA (p.Pro5delinsLeuTer) | C1orf105 | Pathogenic/Likely pathogenic | criteria provided, single submitter |
| 471151 | NM_153747.2(PIGC):c.566T>G (p.Leu189Trp) | C1orf105 | Likely pathogenic | criteria provided, single submitter |
| 471154 | NM_153747.2(PIGC):c.635T>C (p.Leu212Pro) | C1orf105 | Likely pathogenic | criteria provided, single submitter |
| 190451 | NM_153747.2(PIGC):c.659T>C (p.Leu220Pro) | C1orf105 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 471153 | NM_153747.2(PIGC):c.61C>T (p.Arg21Ter) | PIGC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1029615 | NM_153747.2(PIGC):c.308T>C (p.Ile103Thr) | C1orf105 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1029616 | NM_153747.2(PIGC):c.389C>T (p.Thr130Ile) | C1orf105 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1033524 | NM_153747.2(PIGC):c.739A>G (p.Ser247Gly) | C1orf105 | Uncertain significance | criteria provided, single submitter |
| 1402737 | NM_153747.2(PIGC):c.574C>T (p.Arg192Cys) | C1orf105 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1704034 | NM_153747.2(PIGC):c.286G>A (p.Gly96Arg) | C1orf105 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2434837 | NM_153747.2(PIGC):c.223A>G (p.Met75Val) | C1orf105 | Uncertain significance | criteria provided, single submitter |
| 3254687 | NM_153747.2(PIGC):c.484A>T (p.Ile162Phe) | C1orf105 | Uncertain significance | criteria provided, single submitter |
| 3254725 | NM_153747.2(PIGC):c.881G>T (p.Arg294Met) | C1orf105 | Uncertain significance | criteria provided, single submitter |
| 3306473 | NM_153747.2(PIGC):c.593A>G (p.His198Arg) | C1orf105 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 982966 | NM_153747.2(PIGC):c.138C>A (p.Tyr46Ter) | C1orf105 | Uncertain significance | criteria provided, single submitter |
| 1033525 | NM_153747.2(PIGC):c.812G>A (p.Arg271His) | PIGC | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1327021 | NM_153747.2(PIGC):c.796C>T (p.Pro266Ser) | C1orf105 | Benign | criteria provided, multiple submitters, no conflicts |
| 595495 | NM_153747.2(PIGC):c.267T>C (p.Gly89=) | PIGC | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| PIGC | Strong | Autosomal recessive | glycosylphosphatidylinositol biosynthesis defect 16 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PIGC | Orphanet:88616 | Autosomal recessive non-syndromic intellectual disability |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PIGC | HGNC:8960 | ENSG00000135845 | Q92535 | Phosphatidylinositol N-acetylglucosaminyltransferase subunit C | gencc,clinvar |
| C1orf105 | HGNC:29591 | ENSG00000180999 | O95561 | Uncharacterized protein C1orf105 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PIGC | Phosphatidylinositol N-acetylglucosaminyltransferase subunit C | Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI bi… |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 2 | 1.8× | 0.312 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PIGC | Other/Unknown | no | Plno_GlcNAc_GPI2 | |
| C1orf105 | Other/Unknown | no | DUF4548 |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| calcaneal tendon | 1 |
| skin of abdomen | 1 |
| skin of leg | 1 |
| left testis | 1 |
| male germ cell | 1 |
| sperm | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PIGC | 288 | ubiquitous | marker | calcaneal tendon, skin of leg, skin of abdomen |
| C1orf105 | 139 | tissue_specific | marker | sperm, male germ cell, left testis |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PIGC | 794 |
| C1orf105 | 199 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| C1orf105 | PIGC | string_interaction |
Structural data
PDB: 0 · AlphaFold-only: 2 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| PIGC | Q92535 | 88.98 |
| C1orf105 | O95561 | 57.57 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Synthesis of glycosylphosphatidylinositol (GPI) | 1 | 634.4× | 0.002 | PIGC |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| GPI anchor biosynthetic process | 1 | 495.6× | 0.002 | PIGC |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PIGC | 0 | 0 |
| C1orf105 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | PIGC, C1orf105 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PIGC | 0 | — |
| C1orf105 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.