Maturity-onset diabetes of the young type 11

Summary

Maturity-onset diabetes of the young type 11 (MONDO:0013242) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 123

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	maturity-onset diabetes of the young type 11
Mondo ID	MONDO:0013242
OMIM	613375
DOID	DOID:0111109
SNOMED CT	609578001
UMLS	C3150618
MedGen	461968
GARD	0015653
Is cancer (heuristic)	no

Also known as: BLK maturity-onset diabetes of the young (disease) · maturity-onset diabetes of the young (disease) caused by mutation in BLK · maturity-onset diabetes of the young, type 11 · MODY11

Data availability: 123 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder › diabetes mellitus › monogenic diabetes › maturity-onset diabetes of the young › maturity-onset diabetes of the young type 11

Related subtypes (14): maturity-onset diabetes of the young type 1, maturity-onset diabetes of the young type 2, renal cysts and diabetes syndrome, maturity-onset diabetes of the young type 3, maturity-onset diabetes of the young type 4, maturity-onset diabetes of the young type 6, maturity-onset diabetes of the young type 8, maturity-onset diabetes of the young type 7, maturity-onset diabetes of the young type 9, maturity-onset diabetes of the young type 10, Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young, maturity-onset diabetes of the young type 13, maturity-onset diabetes of the young type 14, maturity-onset diabetes of the young, type 12

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

123 retrieved; paginated sample, class counts are floors:

55 uncertain significance, 20 benign, 17 benign/likely benign, 16 conflicting classifications of pathogenicity, 13 likely benign, 1 pathogenic, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
12322	NC_000008.11:g.11474238G>A	FAM167A	Pathogenic	no assertion criteria provided
12320	NM_001715.3(BLK):c.*338T>G	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2428755	NM_001715.3(BLK):c.922A>G (p.Ile308Val)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361474	NM_001715.3(BLK):c.153G>A (p.Pro51=)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361476	NM_001715.3(BLK):c.187G>A (p.Val63Met)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361482	NM_001715.3(BLK):c.617C>G (p.Ser206Cys)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361491	NM_001715.3(BLK):c.1057C>T (p.Arg353Cys)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361492	NM_001715.3(BLK):c.1089G>A (p.Ala363=)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
499795	NM_001715.3(BLK):c.674C>T (p.Pro225Leu)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
619205	NM_001715.3(BLK):c.1075C>T (p.Arg359Cys)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
712998	NM_001715.3(BLK):c.473-7C>G	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909058	NM_001715.3(BLK):c.620-11C>T	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909059	NM_001715.3(BLK):c.668C>T (p.Pro223Leu)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361484	NM_001715.3(BLK):c.672C>T (p.Ala224=)	BLK-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361489	NM_001715.3(BLK):c.974A>C (p.Lys325Thr)	BLK-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910816	NM_001715.3(BLK):c.980A>T (p.Asp327Val)	BLK-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
619201	NM_001715.3(BLK):c.391C>T (p.Arg131Trp)	LOC126860303	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029524	NM_001715.3(BLK):c.84C>A (p.Val28=)	BLK	Uncertain significance	criteria provided, single submitter
12323	NC_000008.11:g.11564613G>T	BLK	no classifications from unflagged records	no classifications from unflagged records
128524	NM_001715.3(BLK):c.139C>G (p.Leu47Val)	BLK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1337092	NM_001715.3(BLK):c.539G>A (p.Arg180His)	BLK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1503499	NM_001715.3(BLK):c.809C>T (p.Thr270Met)	BLK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803104	NM_001715.3(BLK):c.868G>T (p.Ala290Ser)	BLK	Uncertain significance	criteria provided, single submitter
2428692	NM_001715.3(BLK):c.1393T>C (p.Tyr465His)	BLK	Uncertain significance	criteria provided, single submitter
2439526	NM_001715.3(BLK):c.1370C>T (p.Pro457Leu)	BLK	Uncertain significance	criteria provided, single submitter
2580178	NM_001715.3(BLK):c.1171G>A (p.Ala391Thr)	BLK	Uncertain significance	criteria provided, single submitter
3340532	NM_001715.3(BLK):c.237G>A (p.Met79Ile)	BLK	Uncertain significance	criteria provided, single submitter
3382055	NM_001715.3(BLK):c.1013T>C (p.Ile338Thr)	BLK	Uncertain significance	criteria provided, multiple submitters, no conflicts
3595039	NM_001715.3(BLK):c.437G>C (p.Gly146Ala)	BLK	Uncertain significance	criteria provided, single submitter
361467	NM_001715.3(BLK):c.-203C>T	BLK	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
BLK	Supportive	Autosomal dominant	maturity-onset diabetes of the young	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gencc,clinvar
FAM167A	HGNC:15549	ENSG00000154319	Q96KS9	Protein FAM167A	clinvar
BLK-AS1	HGNC:58190	ENSG00000269954		BLK antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
FAM167A	Other/Unknown	no		FAM167, FAM167_domain
BLK-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 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
lymph node	2
male germ line stem cell (sensu Vertebrata) in testis	2
spleen	2
islet of Langerhans	1
secondary oocyte	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
FAM167A	207	broad	marker	stromal cell of endometrium, islet of Langerhans, secondary oocyte
BLK-AS1	124		marker	male germ line stem cell (sensu Vertebrata) in testis, lymph node, spleen

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BLK	2,967
FAM167A	796
BLK-AS1	0

Intra-cohort edges

A	B	Sources
BLK	FAM167A	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BLK	P51451	81.89
FAM167A	Q96KS9	71.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 3 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
RUNX1 regulates transcription of genes involved in BCR signaling	1	1903.3×	0.005	BLK
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.009	BLK
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.009	BLK
Transcriptional regulation by RUNX1	1	146.4×	0.015	BLK
Adaptive Immune System	1	29.8×	0.060	BLK
RNA Polymerase II Transcription	1	22.5×	0.067	BLK
Gene expression (Transcription)	1	17.8×	0.072	BLK
Generic Transcription Pathway	1	15.1×	0.074	BLK
Immune System	1	13.0×	0.077	BLK

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
peptidyl-tyrosine phosphorylation	1	421.3×	0.007	BLK
B cell receptor signaling pathway	1	401.2×	0.007	BLK
positive regulation of insulin secretion	1	255.3×	0.008	BLK
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.009	BLK
intracellular signal transduction	1	38.1×	0.031	BLK
cell differentiation	1	29.1×	0.034	BLK

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
BLK	AFATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BLK	62	4
FAM167A	0	0
BLK-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK
CANERTINIB	3	BLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BLK	483	Binding:477, ADMET:4, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLK	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BLK	483

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

30 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)
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK
CANERTINIB	3	BLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BLK
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	FAM167A, BLK-AS1

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)
FAM167A	0	BLK
BLK-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.