sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Summary

sulfite oxidase deficiency due to molybdenum cofactor deficiency type C (MONDO:0014212) is a disease caused by GPHN (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GPHN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 821

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
Mondo ID	MONDO:0014212
MeSH	C565374
OMIM	615501
Orphanet	308400
DOID	DOID:0111166
UMLS	C1854990
MedGen	340761
GARD	0017388
Is cancer (heuristic)	no

Also known as: combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type C · MOCOD type C · MOCODC · molybdenum cofactor deficiency C · molybdenum cofactor deficiency, complementation group C · molybdenum cofactor deficiency, complementation group type C

Data availability: 821 ClinVar variants · 4 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 › inborn metal metabolism disorder › sulfite oxidase deficiency due to molybdenum cofactor deficiency › sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Related subtypes (3): sulfite oxidase deficiency due to molybdenum cofactor deficiency type A, sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1, sulfite oxidase deficiency due to molybdenum cofactor deficiency type B2

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

600 retrieved; paginated sample, class counts are floors:

265 uncertain significance, 265 likely benign, 41 pathogenic, 16 likely pathogenic, 9 benign, 3 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069066	NM_020806.5(GPHN):c.1156_1159dup (p.Val387fs)	GPHN	Pathogenic	criteria provided, single submitter
1075236	NC_000014.8:g.(?67243172)(67291294_?)del	GPHN	Pathogenic	criteria provided, single submitter
1309047	NM_020806.5(GPHN):c.577_578del (p.Leu193fs)	GPHN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452267	NM_020806.5(GPHN):c.1907dup (p.Gly637fs)	GPHN	Pathogenic	criteria provided, single submitter
1454068	NM_020806.5(GPHN):c.1234C>T (p.Arg412Ter)	GPHN	Pathogenic	criteria provided, single submitter
1456691	NC_000014.8:g.(?67490330)(67555812_?)del	GPHN	Pathogenic	criteria provided, single submitter
1456692	NC_000014.8:g.(?67147805)(67291304_?)del	GPHN	Pathogenic	criteria provided, single submitter
1456696	NC_000014.8:g.(?67346637)(67432062_?)del	GPHN	Pathogenic	criteria provided, single submitter
1457557	NC_000014.8:g.(?67147805)(67243259_?)del	GPHN	Pathogenic	criteria provided, single submitter
1458284	NC_000014.8:g.(?67243162)(67490412_?)del	GPHN	Pathogenic	criteria provided, single submitter
1458569	NM_020806.5(GPHN):c.277C>T (p.Arg93Ter)	GPHN	Pathogenic	criteria provided, single submitter
1459461	NC_000014.8:g.(?67525346)(67567648_?)del	GPHN	Pathogenic	criteria provided, single submitter
1459465	NC_000014.8:g.(?67382700)(67432062_?)del	GPHN	Pathogenic	criteria provided, single submitter
2014914	NM_020806.5(GPHN):c.770_771del (p.His257fs)	GPHN	Pathogenic	criteria provided, single submitter
2021431	NM_020806.5(GPHN):c.802_803insG (p.Tyr268Ter)	GPHN	Pathogenic	criteria provided, single submitter
2028217	NM_020806.5(GPHN):c.630dup (p.Gln211fs)	GPHN	Pathogenic	criteria provided, single submitter
2033928	NM_020806.5(GPHN):c.747del (p.Ser250fs)	GPHN	Pathogenic	criteria provided, single submitter
2036462	NM_020806.5(GPHN):c.1560del (p.Thr520_Val521insTer)	GPHN	Pathogenic	criteria provided, single submitter
2049457	NM_020806.5(GPHN):c.1206del (p.Ala403fs)	GPHN	Pathogenic	criteria provided, single submitter
2059907	NM_020806.5(GPHN):c.168C>A (p.Tyr56Ter)	GPHN	Pathogenic	criteria provided, single submitter
2091794	NM_020806.5(GPHN):c.1702C>T (p.Gln568Ter)	GPHN	Pathogenic	criteria provided, single submitter
2120712	NM_020806.5(GPHN):c.400G>A (p.Gly134Arg)	GPHN	Pathogenic	criteria provided, single submitter
2137597	NM_020806.5(GPHN):c.1223G>A (p.Gly408Asp)	GPHN	Pathogenic	criteria provided, single submitter
2426603	NC_000014.8:g.(?67635630)(67635773_?)del	GPHN	Pathogenic	criteria provided, single submitter
2426605	NC_000014.8:g.(?67567553)(67589114_?)del	GPHN	Pathogenic	criteria provided, single submitter
2426606	NC_000014.8:g.(?67147805)(67391029_?)del	GPHN	Pathogenic	criteria provided, single submitter
2426607	NC_000014.8:g.(?67631859)(67635773_?)del	GPHN	Pathogenic	criteria provided, single submitter
2426608	NC_000014.8:g.(?67291172)(67490412_?)del	GPHN	Pathogenic	criteria provided, single submitter
2724038	NM_020806.5(GPHN):c.1156C>T (p.Arg386Ter)	GPHN	Pathogenic	criteria provided, single submitter
2734795	NM_020806.5(GPHN):c.1275dup (p.Ser426fs)	GPHN	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
GPHN	Strong	Autosomal recessive	sulfite oxidase deficiency due to molybdenum cofactor deficiency type C	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GPHN	Orphanet:308400	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
GPHN	Orphanet:3197	Hereditary hyperekplexia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GPHN	HGNC:15465	ENSG00000171723	Q9NQX3	Gephyrin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GPHN	Gephyrin	Microtubule-associated protein involved in membrane protein-cytoskeleton interactions.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GPHN	Other/Unknown	no		MoaB/Mog_dom, MoeA_linker/N, MoeA_C_domain_IV

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GPHN	270	ubiquitous	marker	cerebellar cortex, cerebellar hemisphere, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GPHN	2,500

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GPHN	Q9NQX3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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
Molybdenum cofactor biosynthesis	1	1631.4×	6e-04	GPHN

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
glycine receptor clustering	1	16852.0×	5e-04	GPHN
establishment of synaptic specificity at neuromuscular junction	1	8426.0×	5e-04	GPHN
gamma-aminobutyric acid receptor clustering	1	3370.4×	8e-04	GPHN
Mo-molybdopterin cofactor biosynthetic process	1	2407.4×	8e-04	GPHN
response to metal ion	1	1532.0×	0.001	GPHN
neurotransmitter receptor localization to postsynaptic specialization membrane	1	802.5×	0.002	GPHN
establishment of protein localization	1	432.1×	0.003	GPHN
synapse assembly	1	230.8×	0.004	GPHN

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 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
GPHN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	GPHN

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GPHN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.