Inherited distal renal tubular acidosis

Summary

Inherited distal renal tubular acidosis (MONDO:1060161) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited distal renal tubular acidosis
Mondo ID	MONDO:1060161
OMIM	179800
GARD	0028168
Is cancer (heuristic)	no

Data availability: 7 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › distal renal tubular acidosis › inherited distal renal tubular acidosis

Related subtypes (1): acquired distal renal tubular acidosis

Subtypes (2): autosomal dominant distal renal tubular acidosis, autosomal recessive distal renal tubular acidosis

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

7 retrieved; paginated sample, class counts are floors:

7 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4533255	NM_000342.4(SLC4A1):c.1806_1847del (p.Arg603_Ile616del)	SLC4A1	Pathogenic	criteria provided, single submitter
4533256	NM_000342.4(SLC4A1):c.1809_1858del (p.Val604fs)	SLC4A1	Pathogenic	criteria provided, single submitter
4533257	NM_000342.4(SLC4A1):c.1102_1118del (p.Pro368fs)	SLC4A1	Pathogenic	criteria provided, single submitter
4533258	NM_000342.4(SLC4A1):c.1164_1180del (p.Arg389fs)	SLC4A1	Pathogenic	criteria provided, single submitter
4533259	NM_000342.4(SLC4A1):c.1805_1866del (p.Arg602fs)	SLC4A1	Pathogenic	criteria provided, single submitter
4533260	NM_000342.4(SLC4A1):c.1805_1832del (p.Arg602fs)	SLC4A1	Pathogenic	criteria provided, single submitter
4533261	NM_000342.4(SLC4A1):c.1096G>A (p.Gly366Arg)	SLC4A1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC4A1	Orphanet:3202	Dehydrated hereditary stomatocytosis
SLC4A1	Orphanet:398088	Hereditary cryohydrocytosis with normal stomatin
SLC4A1	Orphanet:822	Hereditary spherocytosis
SLC4A1	Orphanet:93608	Autosomal dominant distal renal tubular acidosis
SLC4A1	Orphanet:93610	Distal renal tubular acidosis with anemia
SLC4A1	Orphanet:98868	Southeast Asian ovalocytosis

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
SLC4A1	HGNC:11027	ENSG00000004939	P02730	Band 3 anion transport protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC4A1	Band 3 anion transport protein	Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein.

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)
SLC4A1	Other/Unknown	no		Anion_exchange, Anion_exchange_1, HCO3_transpt_euk

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
bone marrow	1
bone marrow cell	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC4A1	161	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC4A1	1,598

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC4A1	P02730	54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tubular acidosis (dRTA) and dRTA with hemolytic anemia (dRTA-HA)	1	11420.0×	1e-03	SLC4A1
Erythrocytes take up oxygen and release carbon dioxide	1	1268.9×	0.002	SLC4A1
O2/CO2 exchange in erythrocytes	1	1268.9×	0.002	SLC4A1
Bicarbonate transporters	1	1142.0×	0.002	SLC4A1
Erythrocytes take up carbon dioxide and release oxygen	1	878.5×	0.003	SLC4A1
SLC transporter disorders	1	203.9×	0.009	SLC4A1
Disorders of transmembrane transporters	1	139.3×	0.011	SLC4A1
R-HSA-425393	1	129.8×	0.011	SLC4A1
SLC-mediated transmembrane transport	1	59.2×	0.021	SLC4A1
Transport of small molecules	1	25.1×	0.044	SLC4A1
Disease	1	13.1×	0.076	SLC4A1

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
response to increased oxygen levels	1	16852.0×	4e-04	SLC4A1
pH elevation	1	16852.0×	4e-04	SLC4A1
intracellular monoatomic ion homeostasis	1	4213.0×	9e-04	SLC4A1
negative regulation of urine volume	1	4213.0×	9e-04	SLC4A1
negative regulation of glycolytic process through fructose-6-phosphate	1	2808.7×	0.001	SLC4A1
plasma membrane phospholipid scrambling	1	1532.0×	0.002	SLC4A1
monoatomic anion transport	1	1404.3×	0.002	SLC4A1
bicarbonate transport	1	802.5×	0.002	SLC4A1
regulation of intracellular pH	1	601.9×	0.003	SLC4A1
erythrocyte development	1	526.6×	0.003	SLC4A1
chloride transport	1	455.5×	0.003	SLC4A1
chloride transmembrane transport	1	237.3×	0.005	SLC4A1
blood coagulation	1	173.7×	0.006	SLC4A1
transmembrane transport	1	168.5×	0.006	SLC4A1
protein localization to plasma membrane	1	108.7×	0.009	SLC4A1

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
SLC4A1	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	SLC4A1

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)
SLC4A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.