Renal tubular acidosis

Summary

Renal tubular acidosis (MONDO:0001909) is a disease (an umbrella term covering 5 Mondo subtypes) with 6 cohort genes.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 6
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	renal tubular acidosis
Mondo ID	MONDO:0001909
MeSH	D000141
DOID	DOID:14219
ICD-11	1272869150
SNOMED CT	1776003
UMLS	C0001126
MedGen	90
GARD	0007552
Anatomy (UBERON)	UBERON:0009773
Is cancer (heuristic)	no

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › disorder of acid-base balance › acidosis disorder › renal tubular acidosis

Related subtypes (2): metabolic acidosis, alcoholic ketoacidosis

Subtypes (5): proximal renal tubular acidosis, renal tubular acidosis 3, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, neuroaxonal dystrophy renal tubular acidosis, hyperkalemic 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

10 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
988216	NM_001692.4(ATP6V1B1):c.79C>T (p.Gln27Ter)	ATP6V1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
8592	NM_001126108.2(SLC12A3):c.1046C>T (p.Pro349Leu)	SLC12A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17764	NM_000342.4(SLC4A1):c.1765C>T (p.Arg589Cys)	SLC4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
235293	NM_000342.4(SLC4A1):c.1825G>A (p.Gly609Arg)	SLC4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
852567	NM_001692.4(ATP6V1B1):c.1181G>A (p.Arg394Gln)	ATP6V1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3902429	NM_001126108.2(SLC12A3):c.2648T>C (p.Leu883Pro)	SLC12A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
694733	NM_001128831.4(CA1):c.368_369del (p.His123fs)	CA1	Uncertain significance	criteria provided, single submitter
830363	NM_000183.3(HADHB):c.110-2324G>C	HADHB	Uncertain significance	criteria provided, single submitter
988235	NM_000342.4(SLC4A1):c.2614G>A (p.Val872Ile)	SLC4A1	Uncertain significance	criteria provided, single submitter
988236	NM_000342.4(SLC4A1):c.2385G>A (p.Met795Ile)	SLC4A1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 11 · 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
WDR72	Limited	Autosomal recessive	renal tubular acidosis	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR72	Orphanet:100033	Hypomaturation amelogenesis imperfecta
WDR72	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
SLC12A3	Orphanet:358	Gitelman syndrome
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
HADHB	Orphanet:746	Mitochondrial trifunctional protein deficiency
ATP6V1B1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR72	HGNC:26790	ENSG00000166415	Q3MJ13	WD repeat-containing protein 72	gencc
SLC12A3	HGNC:10912	ENSG00000070915	P55017	Solute carrier family 12 member 3	clinvar
SLC4A1	HGNC:11027	ENSG00000004939	P02730	Band 3 anion transport protein	clinvar
CA1	HGNC:1368	ENSG00000133742	P00915	Carbonic anhydrase 1	clinvar
HADHB	HGNC:4803	ENSG00000138029	P55084	Trifunctional enzyme subunit beta, mitochondrial	clinvar
ATP6V1B1	HGNC:853	ENSG00000116039	P15313	V-type proton ATPase subunit B, kidney isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR72	WD repeat-containing protein 72	Plays a major role in formation of tooth enamel.
SLC12A3	Solute carrier family 12 member 3	Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules.
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.
CA1	Carbonic anhydrase 1	Catalyzes the reversible hydration of carbon dioxide.
HADHB	Trifunctional enzyme subunit beta, mitochondrial	Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway.
ATP6V1B1	V-type proton ATPase subunit B, kidney isoform	Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.17

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
Scaffold/PPI	1	2.9×	0.458
Enzyme (other)	1	2.0×	0.458
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR72	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
SLC12A3	Other/Unknown	no		SLC12A3, AA-permease/SLC12A_dom, SLC12A_fam
SLC4A1	Other/Unknown	no		Anion_exchange, Anion_exchange_1, HCO3_transpt_euk
CA1	Enzyme (other)	yes	4.2.1.1	CA_dom, Carbonic_anhydrase_a-class_CS, Carbonic_anhydrase_a-class
HADHB	Other/Unknown	no		Thiolase, Thiolase-like, Thiolase_AS
ATP6V1B1	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
trabecular bone tissue	2
kidney epithelium	1
pancreatic ductal cell	1
renal medulla	1
adult mammalian kidney	1
kidney	1
nephron tubule	1
bone marrow	1
bone marrow cell	1
colonic mucosa	1
mucosa of transverse colon	1
deltoid	1
heart right ventricle	1
left ventricle myocardium	1
male germ line stem cell (sensu Vertebrata) in testis	1
metanephros cortex	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR72	139	tissue_specific	marker	kidney epithelium, pancreatic ductal cell, renal medulla
SLC12A3	85	tissue_specific	marker	adult mammalian kidney, nephron tubule, kidney
SLC4A1	161	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
CA1	177	tissue_specific	marker	mucosa of transverse colon, trabecular bone tissue, colonic mucosa
HADHB	295	ubiquitous	marker	heart right ventricle, left ventricle myocardium, deltoid
ATP6V1B1	152	broad	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HADHB	4,047
ATP6V1B1	2,172
CA1	1,800
SLC4A1	1,598
SLC12A3	1,365
WDR72	1,126

Intra-cohort edges

A	B	Sources
ATP6V1B1	CA1	string_interaction
ATP6V1B1	SLC4A1	string_interaction
HADHB	SLC4A1	biogrid_interaction

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CA1	P00915	56
SLC4A1	P02730	54
SLC12A3	P55017	12
HADHB	P55084	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP6V1B1	P15313	87.21
WDR72	Q3MJ13	67.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 6 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Erythrocytes take up oxygen and release carbon dioxide	2	507.6×	9e-05	SLC4A1, CA1
O2/CO2 exchange in erythrocytes	2	507.6×	9e-05	SLC4A1, CA1
Erythrocytes take up carbon dioxide and release oxygen	2	351.4×	1e-04	SLC4A1, CA1
SLC transporter disorders	2	81.6×	0.002	SLC12A3, SLC4A1
Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tubular acidosis (dRTA) and dRTA with hemolytic anemia (dRTA-HA)	1	2284.0×	0.002	SLC4A1
Defective SLC12A3 causes Gitelman syndrome (GS)	1	2284.0×	0.002	SLC12A3
Disorders of transmembrane transporters	2	55.7×	0.002	SLC12A3, SLC4A1
R-HSA-425393	2	51.9×	0.002	SLC12A3, SLC4A1
Transport of small molecules	3	15.1×	0.002	SLC12A3, SLC4A1, CA1
Beta oxidation of myristoyl-CoA to lauroyl-CoA	1	761.3×	0.004	HADHB
Beta oxidation of palmitoyl-CoA to myristoyl-CoA	1	761.3×	0.004	HADHB
Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA	1	456.8×	0.005	HADHB
Beta oxidation of octanoyl-CoA to hexanoyl-CoA	1	456.8×	0.005	HADHB
Beta oxidation of hexanoyl-CoA to butanoyl-CoA	1	456.8×	0.005	HADHB
Acyl chain remodeling of CL	1	380.7×	0.005	HADHB
mitochondrial fatty acid beta-oxidation of unsaturated fatty acids	1	380.7×	0.005	HADHB
Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA	1	380.7×	0.005	HADHB
SLC-mediated transmembrane transport	2	23.7×	0.005	SLC12A3, SLC4A1
Cation-coupled Chloride cotransporters	1	326.3×	0.005	SLC12A3
Bicarbonate transporters	1	228.4×	0.007	SLC4A1
Reversible hydration of carbon dioxide	1	190.3×	0.008	CA1
Interleukin-12 family signaling	1	95.2×	0.016	CA1
Interleukin-12 signaling	1	81.6×	0.018	CA1
Insulin receptor recycling	1	76.1×	0.018	ATP6V1B1
Transferrin endocytosis and recycling	1	73.7×	0.018	ATP6V1B1
ROS and RNS production in phagocytes	1	67.2×	0.019	ATP6V1B1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	60.1×	0.021	CA1
Amino acids regulate mTORC1	1	40.1×	0.030	ATP6V1B1
Ion channel transport	1	19.2×	0.058	ATP6V1B1
Disease	2	5.2×	0.058	SLC12A3, 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
chloride ion homeostasis	2	510.7×	3e-04	SLC12A3, ATP6V1B1
potassium ion homeostasis	2	255.3×	6e-04	SLC12A3, ATP6V1B1
response to increased oxygen levels	1	2808.7×	0.004	SLC4A1
pH elevation	1	2808.7×	0.004	SLC4A1
chloride transmembrane transport	2	79.1×	0.004	SLC12A3, SLC4A1
renal tubular secretion	1	936.2×	0.007	ATP6V1B1
renal sodium ion transport	1	702.2×	0.007	ATP6V1B1
intracellular monoatomic ion homeostasis	1	702.2×	0.007	SLC4A1
negative regulation of urine volume	1	702.2×	0.007	SLC4A1
renal sodium excretion	1	702.2×	0.007	ATP6V1B1
protein localization to plasma membrane	2	36.2×	0.007	SLC4A1, WDR72
vacuolar proton-transporting V-type ATPase complex assembly	1	468.1×	0.008	ATP6V1B1
negative regulation of glycolytic process through fructose-6-phosphate	1	468.1×	0.008	SLC4A1
response to fructose	1	401.2×	0.008	CA1
pH reduction	1	401.2×	0.008	ATP6V1B1
response to salt	1	351.1×	0.009	SLC12A3
olfactory behavior	1	312.1×	0.010	ATP6V1B1
response to aldosterone	1	280.9×	0.010	SLC12A3
plasma membrane phospholipid scrambling	1	255.3×	0.010	SLC4A1
monoatomic anion transport	1	234.1×	0.010	SLC4A1
regulation of pH	1	234.1×	0.010	ATP6V1B1
renal sodium ion absorption	1	165.2×	0.014	SLC12A3
sodium ion homeostasis	1	156.0×	0.014	SLC12A3
synaptic vesicle lumen acidification	1	156.0×	0.014	ATP6V1B1
prostaglandin metabolic process	1	140.4×	0.014	ATP6V1B1
bicarbonate transport	1	133.8×	0.015	SLC4A1
vacuolar acidification	1	122.1×	0.015	ATP6V1B1
biomineral tissue development	1	108.0×	0.017	WDR72
cell volume homeostasis	1	100.3×	0.017	SLC12A3
regulation of intracellular pH	1	100.3×	0.017	SLC4A1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
CA1	METHAZOLAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CA1	70	4
WDR72	0	0
SLC12A3	0	0
SLC4A1	0	0
HADHB	0	0
ATP6V1B1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
METHAZOLAMIDE	4	CA1
ACETAZOLAMIDE	4	CA1
ZONISAMIDE	4	CA1
TRICHLORMETHIAZIDE	4	CA1
CHLORTHALIDONE	4	CA1
ACETAMINOPHEN	4	CA1
NITROUS ACID	4	CA1
CELECOXIB	4	CA1
SULFUR	4	CA1
LEVETIRACETAM	4	CA1
SODIUM ACETATE	4	CA1
PHENOL	4	CA1
DICHLORPHENAMIDE	4	CA1
ETHOXZOLAMIDE	4	CA1
SULFANILAMIDE	4	CA1
VERALIPRIDE	4	CA1
DORZOLAMIDE	4	CA1
BRINZOLAMIDE	4	CA1
TOPIRAMATE	4	CA1
NILOTINIB	4	CA1
SULPIRIDE	4	CA1
BORTEZOMIB	4	CA1
SULTHIAME	4	CA1
FUROSEMIDE	4	CA1
INDAPAMIDE	4	CA1
MAFENIDE	4	CA1
SULFASALAZINE	4	CA1
SALICYLIC ACID	4	CA1
HYDROCHLOROTHIAZIDE	4	CA1
TAVABOROLE	4	CA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CA1	886	Binding:852, ADMET:32, Functional:2
HADHB	2	Binding:2
SLC12A3	1	Functional:1
ATP6V1B1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CA1	4.2.1.1	carbonic anhydrase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CA1	886

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
METHAZOLAMIDE	4	CA1
ACETAZOLAMIDE	4	CA1
ZONISAMIDE	4	CA1
TRICHLORMETHIAZIDE	4	CA1
CHLORTHALIDONE	4	CA1
ACETAMINOPHEN	4	CA1
NITROUS ACID	4	CA1
CELECOXIB	4	CA1
SULFUR	4	CA1
LEVETIRACETAM	4	CA1
SODIUM ACETATE	4	CA1
PHENOL	4	CA1
DICHLORPHENAMIDE	4	CA1
ETHOXZOLAMIDE	4	CA1
SULFANILAMIDE	4	CA1
VERALIPRIDE	4	CA1
DORZOLAMIDE	4	CA1
BRINZOLAMIDE	4	CA1
TOPIRAMATE	4	CA1
NILOTINIB	4	CA1
SULPIRIDE	4	CA1
BORTEZOMIB	4	CA1
SULTHIAME	4	CA1
FUROSEMIDE	4	CA1
INDAPAMIDE	4	CA1
MAFENIDE	4	CA1
SULFASALAZINE	4	CA1
SALICYLIC ACID	4	CA1
HYDROCHLOROTHIAZIDE	4	CA1
TAVABOROLE	4	CA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CA1
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	5	WDR72, SLC12A3, SLC4A1, HADHB, ATP6V1B1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WDR72	0	—
SLC12A3	1	—
SLC4A1	0	—
HADHB	2	—
ATP6V1B1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.