Diabetes mellitus, transient neonatal, 1

Summary

Diabetes mellitus, transient neonatal, 1 (MONDO:0011073) is a disease caused by ZFP57 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Europe) [Orphanet-validated]
• Causal gene: ZFP57 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 45
• Phenotypes (HPO): 23

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.3	Europe	Validated

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0001518	Small for gestational age	Very frequent (80-99%)
HP:0001944	Dehydration	Very frequent (80-99%)
HP:0003074	Hyperglycemia	Very frequent (80-99%)
HP:0040216	Hypoinsulinemia	Very frequent (80-99%)
HP:0000158	Macroglossia	Frequent (30-79%)
HP:0001537	Umbilical hernia	Frequent (30-79%)
HP:0004904	Maturity-onset diabetes of the young	Frequent (30-79%)
HP:0008255	Transient neonatal diabetes mellitus	Frequent (30-79%)
HP:0000077	Abnormality of the kidney	Occasional (5-29%)
HP:0000079	Abnormality of the urinary system	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000707	Abnormality of the nervous system	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0009800	Maternal diabetes	Occasional (5-29%)
HP:0012758	Neurodevelopmental delay	Occasional (5-29%)
HP:0040064	Abnormality of limbs	Occasional (5-29%)
HP:0030057	Autoimmune antibody positivity	Excluded (0%)
HP:0001953	Diabetic ketoacidosis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	diabetes mellitus, transient neonatal, 1
Mondo ID	MONDO:0011073
MeSH	C563322
OMIM	601410
Orphanet	99886
DOID	DOID:0061173
SNOMED CT	609579009
UMLS	C1832386
MedGen	371317
GARD	0001839
Is cancer (heuristic)	no

Also known as: diabetes mellitus, transient neonatal 1 · diabetes mellitus, transient neonatal, 1 · diabetes mellitus, transient neonatal, type 1

Data availability: 45 ClinVar variants · 5 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 › neonatal diabetes mellitus › transient neonatal diabetes mellitus › diabetes mellitus, transient neonatal, 1

Related subtypes (2): diabetes mellitus, transient neonatal, 2, diabetes mellitus, transient neonatal, 3

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

45 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 9 conflicting classifications of pathogenicity, 8 pathogenic, 6 benign/likely benign, 5 benign, 2 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323781	NM_001109809.5(ZFP57):c.133del (p.Thr45fs)	ZFP57	Pathogenic	criteria provided, single submitter
715	NM_001109809.2(ZFP57):c.783C>A (p.Cys261Ter)	ZFP57	Pathogenic	no assertion criteria provided
716	NM_001109809.5(ZFP57):c.317_318del (p.Glu106fs)	ZFP57	Pathogenic	no assertion criteria provided
717	NM_001109809.5(ZFP57):c.1383del (p.Tyr462fs)	ZFP57	Pathogenic	no assertion criteria provided
718	NM_001109809.5(ZFP57):c.1372C>G (p.His458Asp)	ZFP57	Pathogenic	no assertion criteria provided
719	NM_001109809.5(ZFP57):c.743G>A (p.Arg248His)	ZFP57	Pathogenic	no assertion criteria provided
720	NM_001109809.5(ZFP57):c.829C>A (p.His277Asn)	ZFP57	Pathogenic	no assertion criteria provided
721	NM_001109809.5(ZFP57):c.898_905del (p.Gly299_Thr300insTer)	ZFP57	Pathogenic	no assertion criteria provided
1325370	NM_001109809.5(ZFP57):c.711dup (p.Lys238fs)	ZFP57	Likely pathogenic	criteria provided, single submitter
3048727	NM_001109809.5(ZFP57):c.448C>T (p.Gln150Ter)	ZFP57	Likely pathogenic	criteria provided, single submitter
130769	NM_001109809.5(ZFP57):c.1118C>G (p.Ser373Cys)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
130770	NM_001109809.5(ZFP57):c.113G>A (p.Arg38Gln)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
130774	NM_001109809.5(ZFP57):c.374G>A (p.Arg125Gln)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356211	NM_001109809.5(ZFP57):c.1472C>G (p.Thr491Ser)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356217	NM_001109809.5(ZFP57):c.495G>A (p.Val165=)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356219	NM_001109809.5(ZFP57):c.475A>T (p.Thr159Ser)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904449	NM_001109809.5(ZFP57):c.1033G>C (p.Ala345Pro)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
905244	NM_001109809.5(ZFP57):c.532T>C (p.Tyr178His)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
907777	NM_001109809.5(ZFP57):c.1230G>A (p.Pro410=)	ZFP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2665090	NM_001109809.5(ZFP57):c.751C>T (p.Arg251Cys)	ZFP57	Uncertain significance	criteria provided, single submitter
3473390	NM_001109809.5(ZFP57):c.991G>A (p.Glu331Lys)	ZFP57	Uncertain significance	criteria provided, multiple submitters, no conflicts
356212	NM_001109809.5(ZFP57):c.857C>T (p.Pro286Leu)	ZFP57	Uncertain significance	criteria provided, single submitter
356213	NM_001109809.5(ZFP57):c.798G>A (p.Lys266=)	ZFP57	Uncertain significance	criteria provided, single submitter
356214	NM_001109809.5(ZFP57):c.752G>A (p.Arg251His)	ZFP57	Uncertain significance	criteria provided, multiple submitters, no conflicts
356215	NM_001109809.5(ZFP57):c.749G>A (p.Arg250His)	ZFP57	Uncertain significance	criteria provided, multiple submitters, no conflicts
356216	NM_001109809.5(ZFP57):c.553A>G (p.Ser185Gly)	ZFP57	Uncertain significance	criteria provided, single submitter
356220	NM_001109809.5(ZFP57):c.285C>T (p.Thr95=)	ZFP57	Uncertain significance	criteria provided, single submitter
356221	NM_001109809.5(ZFP57):c.277C>G (p.Leu93Val)	ZFP57	Uncertain significance	criteria provided, multiple submitters, no conflicts
3766594	NM_001109809.5(ZFP57):c.1282G>A (p.Val428Ile)	ZFP57	Uncertain significance	criteria provided, single submitter
3892913	NM_001109809.5(ZFP57):c.512C>T (p.Ala171Val)	ZFP57	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
ZFP57	Definitive	Autosomal recessive	diabetes mellitus, transient neonatal, 1	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZFP57	Orphanet:99886	Transient neonatal diabetes mellitus

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
ZFP57	HGNC:18791	ENSG00000204644	Q9NU63	Zinc finger protein 57 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZFP57	Zinc finger protein 57 homolog	Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including D…

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZFP57	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf

Expression context

Cohort genes with no expression data: 0.

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
C1 segment of cervical spinal cord	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZFP57	112	tissue_specific	yes	primordial germ cell in gonad, C1 segment of cervical spinal cord, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZFP57	1,009

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZFP57	Q9NU63	56.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
autosome genomic imprinting	1	2407.4×	8e-04	ZFP57
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ZFP57

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
ZFP57	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	ZFP57

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)
ZFP57	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.