methylmalonic aciduria and homocystinuria, cb1L type

Summary

methylmalonic aciduria and homocystinuria, cb1L type (MONDO:0975798) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	methylmalonic aciduria and homocystinuria, cb1L type
Mondo ID	MONDO:0975798
OMIM	620940
UMLS	C5975387
MedGen	1874917
GARD	0027317
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn organic aciduria › methylmalonic acidemia › methylmalonic aciduria and homocystinuria › methylmalonic aciduria and homocystinuria, cb1L type

Related subtypes (5): methylmalonic aciduria and homocystinuria type cblF, methylmalonic aciduria and homocystinuria type cblC, methylmalonic aciduria and homocystinuria type cblD, methylmalonic acidemia with homocystinuria, type cblX, methylmalonic acidemia with homocystinuria, type cblJ

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
393304	NM_020457.3(THAP11):c.240C>G (p.Phe80Leu)	CENPT	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
CENPT	HGNC:25787	ENSG00000102901	Q96BT3	Centromere protein T	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CENPT	Centromere protein T	Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation.

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)
CENPT	Other/Unknown	no		Histone-fold, CENP-T, CENP-T_N

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
CENPT	181	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CENPT	1,010

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CENPT	Q96BT3	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Nucleosome assembly	1	475.8×	0.021	CENPT
Chromosome Maintenance	1	211.5×	0.021	CENPT
Amplification of signal from the kinetochores	1	196.9×	0.021	CENPT
Deposition of new CENPA-containing nucleosomes at the centromere	1	158.6×	0.021	CENPT
Mitotic Spindle Checkpoint	1	158.6×	0.021	CENPT
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.021	CENPT
Mitotic Metaphase and Anaphase	1	96.8×	0.021	CENPT
Mitotic Anaphase	1	96.8×	0.021	CENPT
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.021	CENPT
Cell Cycle Checkpoints	1	88.5×	0.021	CENPT
Resolution of Sister Chromatid Cohesion	1	86.5×	0.021	CENPT
RHO GTPases Activate Formins	1	77.7×	0.021	CENPT
Mitotic Prometaphase	1	69.2×	0.021	CENPT
RHO GTPase Effectors	1	68.0×	0.021	CENPT
M Phase	1	66.0×	0.021	CENPT
Separation of Sister Chromatids	1	60.7×	0.022	CENPT
Cell Cycle, Mitotic	1	48.2×	0.026	CENPT
Cell Cycle	1	36.0×	0.031	CENPT
Signaling by Rho GTPases	1	34.2×	0.031	CENPT
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.031	CENPT
Signal Transduction	1	10.2×	0.098	CENPT

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
kinetochore assembly	1	1203.7×	0.004	CENPT
chromosome organization	1	581.1×	0.004	CENPT
chromosome segregation	1	173.7×	0.009	CENPT
mitotic cell cycle	1	133.8×	0.009	CENPT
cell division	1	46.2×	0.022	CENPT

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
CENPT	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	CENPT

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)
CENPT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.