Fanconi anemia complementation group T

Summary

Fanconi anemia complementation group T (MONDO:0014638) is a disease caused by UBE2T (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: UBE2T (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group T
Mondo ID	MONDO:0014638
OMIM	616435
DOID	DOID:0111081
UMLS	C4084840
MedGen	896157
GARD	0016111
Is cancer (heuristic)	no

Also known as: Fanconi anaemia caused by mutation in UBE2T · Fanconi anaemia complementation group type T · Fanconi anemia caused by mutation in UBE2T · Fanconi anemia complementation group type T · Fanconi anemia, complementation group T · Fanconi Anemia, complementation group type T · FANCT · UBE2T Fanconi anaemia · UBE2T Fanconi anemia

Data availability: 9 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › Fanconi anemia › Fanconi anemia complementation group T

Related subtypes (21): Fanconi anemia complementation group C, Fanconi anemia complementation group D2, Fanconi anemia complementation group A, Fanconi anemia complementation group B, Fanconi anemia complementation group E, Fanconi anemia complementation group F, Fanconi anemia complementation group D1, Fanconi anemia complementation group I, Fanconi anemia complementation group J, Fanconi anemia complementation group N, Fanconi anemia complementation group O, Fanconi anemia complementation group P, Fanconi anemia complementation group G, Fanconi anemia complementation group L, Fanconi anemia complementation group Q, Fanconi anemia complementation group V, Fanconi anemia complementation group R, Fanconi anemia complementation group U, Fanconi anemia, complementation group W, Fanconi anemia, complementation group S, fanconi anemia, complementation group 10

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

9 retrieved; paginated sample, class counts are floors:

5 pathogenic, 2 benign, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
929630	NM_014176.3(UBE2T):c.-65+1253_*12383del	LGR6	Pathogenic	no assertion criteria provided
199436	NM_014176.4(UBE2T):c.4C>G (p.Gln2Glu)	UBE2T	Pathogenic	criteria provided, single submitter
199437	NM_014176.4(UBE2T):c.179+5G>A	UBE2T	Pathogenic	no assertion criteria provided
929628	NM_014176.4(UBE2T):c.110-280_468+264del	UBE2T	Pathogenic	no assertion criteria provided
929629	NM_014176.4(UBE2T):c.110-280_468+264dup	UBE2T	Pathogenic	no assertion criteria provided
3233393	NM_003325.4(HIRA):c.41A>G (p.Lys14Arg)	HIRA	Uncertain significance	criteria provided, single submitter
4076287	NM_014176.4(UBE2T):c.-65+1729G>A	UBE2T	Uncertain significance	criteria provided, single submitter
1231134	NM_014176.4(UBE2T):c.385-11T>C	UBE2T	Benign	criteria provided, multiple submitters, no conflicts
1269291	NM_014176.4(UBE2T):c.15A>G (p.Ser5=)	UBE2T	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
UBE2T	Strong	Autosomal recessive	Fanconi anemia complementation group T	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UBE2T	Orphanet:84	Fanconi anemia
HIRA	Orphanet:567	22q11.2 deletion syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UBE2T	HGNC:25009	ENSG00000077152	Q9NPD8	Ubiquitin-conjugating enzyme E2 T	gencc,clinvar
LGR6	HGNC:19719	ENSG00000133067	Q9HBX8	Leucine-rich repeat-containing G-protein coupled receptor 6	clinvar
HIRA	HGNC:4916	ENSG00000100084	P54198	Protein HIRA	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UBE2T	Ubiquitin-conjugating enzyme E2 T	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
LGR6	Leucine-rich repeat-containing G-protein coupled receptor 6	Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a marker of multipotent stem cells in the epidermis.
HIRA	Protein HIRA	Cooperates with ASF1A to promote replication-independent chromatin assembly.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.67

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
GPCR	1	8.0×	0.230
Scaffold/PPI	1	5.8×	0.230
Enzyme (other)	1	4.0×	0.230

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UBE2T	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
LGR6	GPCR	yes		GPCR_Rhodpsn, LRRNT, Leu-rich_rpt
HIRA	Scaffold/PPI	no		WD40_rpt, HIRA-like_C, WD40/YVTN_repeat-like_dom_sf

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
oocyte	1
ventricular zone	1
descending thoracic aorta	1
right coronary artery	1
thoracic aorta	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UBE2T	220	ubiquitous	marker	oocyte, ventricular zone, ganglionic eminence
LGR6	201	broad	marker	right coronary artery, descending thoracic aorta, thoracic aorta
HIRA	254	ubiquitous	yes	left lobe of thyroid gland, thyroid gland, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UBE2T	3,706
HIRA	1,692
LGR6	1,099

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UBE2T	Q9NPD8	13
HIRA	P54198	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LGR6	Q9HBX8	77.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	223.9×	0.018	HIRA
Regulation of FZD by ubiquitination	1	173.0×	0.018	LGR6
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	1	122.8×	0.018	UBE2T
Fanconi Anemia Pathway	1	92.8×	0.018	UBE2T
Replacement of protamines by nucleosomes in the male pronucleus	1	90.6×	0.018	HIRA
TCF dependent signaling in response to WNT	1	39.2×	0.030	LGR6
Signaling by WNT	1	37.3×	0.030	LGR6
Signal Transduction	1	3.4×	0.267	LGR6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
bone regeneration	1	1123.5×	0.018	LGR6
protein K29-linked ubiquitination	1	510.7×	0.018	UBE2T
protein K27-linked ubiquitination	1	401.2×	0.018	UBE2T
protein K6-linked ubiquitination	1	330.4×	0.018	UBE2T
muscle cell differentiation	1	280.9×	0.018	HIRA
gastrulation	1	234.1×	0.018	HIRA
negative chemotaxis	1	216.1×	0.018	LGR6
protein K11-linked ubiquitination	1	130.6×	0.024	UBE2T
positive regulation of Wnt signaling pathway	1	127.7×	0.024	LGR6
protein monoubiquitination	1	114.6×	0.024	UBE2T
protein K63-linked ubiquitination	1	89.2×	0.028	UBE2T
protein autoubiquitination	1	78.0×	0.029	UBE2T
DNA-templated transcription	1	74.9×	0.029	HIRA
protein K48-linked ubiquitination	1	56.2×	0.035	UBE2T
positive regulation of canonical Wnt signaling pathway	1	51.5×	0.035	LGR6
nucleosome assembly	1	46.8×	0.035	HIRA
anatomical structure morphogenesis	1	46.4×	0.035	HIRA
osteoblast differentiation	1	40.4×	0.038	HIRA
protein polyubiquitination	1	38.5×	0.038	UBE2T
cell population proliferation	1	34.2×	0.040	LGR6
Wnt signaling pathway	1	33.2×	0.040	LGR6
axon guidance	1	30.2×	0.042	LGR6
chromatin remodeling	1	24.3×	0.049	HIRA
DNA repair	1	21.3×	0.054	UBE2T
positive regulation of cell migration	1	20.6×	0.054	LGR6
DNA damage response	1	17.8×	0.059	UBE2T
G protein-coupled receptor signaling pathway	1	12.1×	0.084	LGR6
regulation of transcription by RNA polymerase II	1	3.9×	0.236	HIRA

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 1

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
UBE2T	ZINC CHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UBE2T	1	4
HIRA	1	2
LGR6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ZINC CHLORIDE	4	UBE2T
MOLIBRESIB	2	HIRA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
UBE2T	15	Binding:15
HIRA	6	Binding:6
LGR6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UBE2T	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 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.

Compound	Max phase	Cohort target (bioactivity)
ZINC CHLORIDE	4	UBE2T
MOLIBRESIB	2	HIRA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	UBE2T
B	Phased (≥1) drug, not yet approved	1	HIRA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	LGR6
E	Difficult family or no structure, no drug	0

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)
LGR6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.