Anencephaly 2

Summary

Anencephaly 2 (MONDO:0030338) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anencephaly 2
Mondo ID	MONDO:0030338
OMIM	619452
UMLS	C5561945
MedGen	1794155
GARD	0027927
Is cancer (heuristic)	no

Also known as: anencephaly 2 · ANPH2

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

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › anencephaly › anencephaly 2

Related subtypes (3): anencephaly 1, hydranencephaly, isolated anencephaly

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184278	NM_030952.3(NUAK2):c.412_433delinsG (p.Tyr138_Gln145delinsGlu)	NUAK2	Pathogenic	no assertion criteria provided
2664206	NM_030952.3(NUAK2):c.310A>T (p.Met104Leu)	NUAK2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
NUAK2	Moderate	Autosomal recessive	anencephaly 2	2

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
NUAK2	HGNC:29558	ENSG00000163545	Q9H093	NUAK family SNF1-like kinase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUAK2	NUAK family SNF1-like kinase 2	Stress-activated kinase involved in tolerance to glucose starvation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NUAK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

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
blood	1
cervix squamous epithelium	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUAK2	220	ubiquitous	marker	cervix squamous epithelium, lower esophagus mucosa, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUAK2	852

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NUAK2	Q9H093	63.45

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
regulation of hippo signaling	1	2407.4×	0.003	NUAK2
protein localization to nucleus	1	351.1×	0.007	NUAK2
cellular response to glucose starvation	1	337.0×	0.007	NUAK2
actin cytoskeleton organization	1	79.1×	0.021	NUAK2
protein phosphorylation	1	68.0×	0.021	NUAK2
negative regulation of apoptotic process	1	34.8×	0.034	NUAK2
apoptotic process	1	28.7×	0.035	NUAK2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
NUAK2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NUAK2	34	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	NUAK2
AXITINIB	4	NUAK2
RUXOLITINIB	4	NUAK2
NERATINIB	4	NUAK2
TOFACITINIB CITRATE	4	NUAK2
TOFACITINIB	4	NUAK2
BOSUTINIB	4	NUAK2
NINTEDANIB	4	NUAK2
SUNITINIB	4	NUAK2
CRIZOTINIB	4	NUAK2
MIDOSTAURIN	4	NUAK2
GEFITINIB	4	NUAK2
BRIVANIB ALANINATE	3	NUAK2
ENZASTAURIN	3	NUAK2
DEFACTINIB	3	NUAK2
LEROCICLIB	3	NUAK2
ALVOCIDIB	3	NUAK2
DOVITINIB	3	NUAK2
LESTAURTINIB	3	NUAK2
RUBOXISTAURIN	3	NUAK2
SU-014813	2	NUAK2
NARAZACICLIB	2	NUAK2
DANUSERTIB	2	NUAK2
R-406	2	NUAK2
TOZASERTIB	2	NUAK2
BMS-754807	2	NUAK2
PELITINIB	2	NUAK2
GSK-461364	1	NUAK2
KW-2449	1	NUAK2
BMS-387032	1	NUAK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NUAK2	200	Binding:200

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NUAK2	200

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

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)
FEDRATINIB	4	NUAK2
AXITINIB	4	NUAK2
RUXOLITINIB	4	NUAK2
NERATINIB	4	NUAK2
TOFACITINIB CITRATE	4	NUAK2
TOFACITINIB	4	NUAK2
BOSUTINIB	4	NUAK2
NINTEDANIB	4	NUAK2
SUNITINIB	4	NUAK2
CRIZOTINIB	4	NUAK2
MIDOSTAURIN	4	NUAK2
GEFITINIB	4	NUAK2
BRIVANIB ALANINATE	3	NUAK2
ENZASTAURIN	3	NUAK2
DEFACTINIB	3	NUAK2
LEROCICLIB	3	NUAK2
ALVOCIDIB	3	NUAK2
DOVITINIB	3	NUAK2
LESTAURTINIB	3	NUAK2
RUBOXISTAURIN	3	NUAK2
SU-014813	2	NUAK2
NARAZACICLIB	2	NUAK2
DANUSERTIB	2	NUAK2
R-406	2	NUAK2
TOZASERTIB	2	NUAK2
BMS-754807	2	NUAK2
PELITINIB	2	NUAK2
GSK-461364	1	NUAK2
KW-2449	1	NUAK2
BMS-387032	1	NUAK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NUAK2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.