Delpire-McNeill syndrome

Summary

Delpire-McNeill syndrome (MONDO:0033667) is a disease caused by SLC12A2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC12A2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 64

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Delpire-McNeill syndrome
Mondo ID	MONDO:0033667
OMIM	619083
Orphanet	633024
UMLS	C5436771
MedGen	1725056
GARD	0018533
Is cancer (heuristic)	no

Also known as: DELMNES · SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome

Data availability: 64 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Delpire-McNeill syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

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

64 retrieved; paginated sample, class counts are floors:

32 uncertain significance, 10 benign/likely benign, 8 likely benign, 5 likely pathogenic, 4 conflicting classifications of pathogenicity, 4 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
984669	NM_001046.3(SLC12A2):c.980C>T (p.Ala327Val)	SLC12A2	Pathogenic	no assertion criteria provided
984670	NM_001046.3(SLC12A2):c.2675G>A (p.Trp892Ter)	SLC12A2	Pathogenic	no assertion criteria provided
984671	NM_001046.3(SLC12A2):c.1127A>T (p.Asn376Ile)	SLC12A2	Pathogenic	no assertion criteria provided
984672	NM_001046.3(SLC12A2):c.555dup (p.His186fs)	SLC12A2	Pathogenic	no assertion criteria provided
1704394	NM_001046.3(SLC12A2):c.2476-1G>C	SLC12A2	Likely pathogenic	criteria provided, single submitter
3601715	NM_001046.3(SLC12A2):c.541G>T (p.Glu181Ter)	SLC12A2	Likely pathogenic	criteria provided, single submitter
3780607	NM_001046.3(SLC12A2):c.3147G>A (p.Trp1049Ter)	SLC12A2	Likely pathogenic	criteria provided, single submitter
3894582	NM_001046.3(SLC12A2):c.352dup (p.Ala118fs)	SLC12A2	Likely pathogenic	criteria provided, single submitter
4292146	NM_001046.3(SLC12A2):c.2160_2163dup (p.Leu722fs)	SLC12A2	Likely pathogenic	criteria provided, single submitter
1385353	NM_001046.3(SLC12A2):c.288GGC[10] (p.Ala105_Ala107dup)	LOC129994526	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1335592	NM_001046.3(SLC12A2):c.953-7C>T	SLC12A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1671022	NM_001046.3(SLC12A2):c.562GGC[6] (p.Gly192dup)	SLC12A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3796424	NM_001046.3(SLC12A2):c.1958G>A (p.Arg653His)	SLC12A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1365125	NM_001046.3(SLC12A2):c.41G>T (p.Gly14Val)	LOC129994526	Uncertain significance	criteria provided, multiple submitters, no conflicts
1440806	NM_001046.3(SLC12A2):c.288GGC[11] (p.Ala104_Ala107dup)	LOC129994526	Uncertain significance	criteria provided, multiple submitters, no conflicts
1510335	NM_001046.3(SLC12A2):c.235A>C (p.Ser79Arg)	LOC129994526	Uncertain significance	criteria provided, multiple submitters, no conflicts
3235029	NM_001046.3(SLC12A2):c.154G>A (p.Asp52Asn)	LOC129994526	Uncertain significance	criteria provided, single submitter
3341336	NM_001046.3(SLC12A2):c.119C>T (p.Pro40Leu)	LOC129994526	Uncertain significance	criteria provided, single submitter
1342498	NM_001046.3(SLC12A2):c.2616+1547G>T	SLC12A2	Uncertain significance	criteria provided, single submitter
1371142	NM_001046.3(SLC12A2):c.1741C>T (p.Pro581Ser)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1373721	NM_001046.3(SLC12A2):c.3622C>G (p.Leu1208Val)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1385672	NM_001046.3(SLC12A2):c.788A>C (p.Glu263Ala)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1401954	NM_001046.3(SLC12A2):c.2293C>G (p.Leu765Val)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1445687	NM_001046.3(SLC12A2):c.2848G>A (p.Val950Met)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1473763	NM_001046.3(SLC12A2):c.2210T>A (p.Leu737Gln)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1476334	NM_001046.3(SLC12A2):c.1127A>G (p.Asn376Ser)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1505967	NM_001046.3(SLC12A2):c.881G>A (p.Arg294His)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679711	NM_001046.3(SLC12A2):c.3566C>T (p.Ala1189Val)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679744	NM_001046.3(SLC12A2):c.1226T>C (p.Ile409Thr)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1709687	NM_001046.3(SLC12A2):c.1076G>A (p.Ser359Asn)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
SLC12A2	Strong	Autosomal dominant	Delpire-McNeill syndrome	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC12A2	Orphanet:633021	SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2	Orphanet:633024	SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome

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
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC12A2	Solute carrier family 12 member 2	Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.

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)
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom

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
inferior vagus X ganglion	1
palpebral conjunctiva	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC12A2	277	ubiquitous	marker	palpebral conjunctiva, parotid gland, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC12A2	2,461

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC12A2	P55011	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Cation-coupled Chloride cotransporters	1	1631.4×	0.002	SLC12A2
R-HSA-425393	1	129.8×	0.015	SLC12A2
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC12A2
Transport of small molecules	1	25.1×	0.040	SLC12A2

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
positive regulation of cell volume	1	16852.0×	7e-04	SLC12A2
inorganic anion import across plasma membrane	1	8426.0×	7e-04	SLC12A2
inorganic cation import across plasma membrane	1	8426.0×	7e-04	SLC12A2
positive regulation of aspartate secretion	1	8426.0×	7e-04	SLC12A2
regulation of matrix metallopeptidase secretion	1	8426.0×	7e-04	SLC12A2
regulation of spontaneous synaptic transmission	1	4213.0×	0.001	SLC12A2
negative regulation of vascular wound healing	1	3370.4×	0.001	SLC12A2
transepithelial ammonium transport	1	3370.4×	0.001	SLC12A2
transepithelial chloride transport	1	1872.4×	0.001	SLC12A2
ammonium transmembrane transport	1	1872.4×	0.001	SLC12A2
hyperosmotic response	1	1685.2×	0.001	SLC12A2
intracellular chloride ion homeostasis	1	1685.2×	0.001	SLC12A2
chloride ion homeostasis	1	1532.0×	0.001	SLC12A2
T cell chemotaxis	1	1123.5×	0.002	SLC12A2
cellular response to potassium ion	1	1053.2×	0.002	SLC12A2
intracellular potassium ion homeostasis	1	991.3×	0.002	SLC12A2
cellular response to chemokine	1	991.3×	0.002	SLC12A2
sodium ion homeostasis	1	936.2×	0.002	SLC12A2
intracellular sodium ion homeostasis	1	766.0×	0.002	SLC12A2
potassium ion homeostasis	1	766.0×	0.002	SLC12A2
sodium ion import across plasma membrane	1	624.1×	0.002	SLC12A2
cell volume homeostasis	1	601.9×	0.002	SLC12A2
gamma-aminobutyric acid signaling pathway	1	543.6×	0.002	SLC12A2
maintenance of blood-brain barrier	1	481.5×	0.003	SLC12A2
potassium ion import across plasma membrane	1	366.4×	0.003	SLC12A2
chloride transmembrane transport	1	237.3×	0.005	SLC12A2
sodium ion transmembrane transport	1	203.0×	0.005	SLC12A2
transport across blood-brain barrier	1	179.3×	0.006	SLC12A2
monoatomic ion transport	1	156.0×	0.006	SLC12A2

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
SLC12A2	BUMETANIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC12A2	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BUMETANIDE	4	SLC12A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC12A2	13	Binding:9, Functional:4

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

1 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)
BUMETANIDE	4	SLC12A2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC12A2
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.