Autosomal recessive distal renal tubular acidosis

Summary

Autosomal recessive distal renal tubular acidosis (MONDO:0018440) is a disease caused by FOXI1 (GenCC Strong), with 4 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: FOXI1 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 109
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive distal renal tubular acidosis
Mondo ID	MONDO:0018440
Orphanet	402041
UMLS	C1864498
MedGen	351142
GARD	0004666
Is cancer (heuristic)	no

Also known as: AR dRTA · autosomal recessive distal renal tubular acidosis (disease) · autosomal recessive distal RTA · distal renal tubular acidosis (disease), autosomal recessive

Data availability: 109 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive distal renal tubular acidosis

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

Subtypes (3): renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, renal tubular acidosis, distal, 4, with hemolytic anemia

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

109 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 23 benign, 18 conflicting classifications of pathogenicity, 9 benign/likely benign, 8 pathogenic/likely pathogenic, 5 likely pathogenic, 4 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179181	NM_020632.3(ATP6V0A4):c.52C>T (p.Gln18Ter)	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, single submitter
1328935	NM_020632.3(ATP6V0A4):c.2257+1G>A	ATP6V0A4	Pathogenic	criteria provided, multiple submitters, no conflicts
384333	NM_020632.3(ATP6V0A4):c.1231G>T (p.Asp411Tyr)	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
423162	NM_020632.3(ATP6V0A4):c.1180+1del	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
450988	NM_020632.3(ATP6V0A4):c.2419C>T (p.Arg807Ter)	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5150	NM_020632.3(ATP6V0A4):c.2257C>T (p.Gln753Ter)	ATP6V0A4	Pathogenic	criteria provided, multiple submitters, no conflicts
5159	NM_020632.3(ATP6V0A4):c.2420G>A (p.Arg807Gln)	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
623151	NM_020632.3(ATP6V0A4):c.1346G>A (p.Arg449His)	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
632498	NM_020632.3(ATP6V0A4):c.2308C>T (p.Arg770Ter)	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802370	NM_020632.3(ATP6V0A4):c.1691+2dup	ATP6V0A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802371	NM_020632.3(ATP6V0A4):c.369_373del (p.Glu123fs)	ATP6V0A4	Pathogenic	criteria provided, single submitter
973549	NM_020632.3(ATP6V0A4):c.2140-61_2257+166del	ATP6V0A4	Pathogenic	criteria provided, single submitter
2691295	NM_020632.3(ATP6V0A4):c.2139+1G>T	ATP6V0A4	Likely pathogenic	criteria provided, single submitter
3063860	NM_020632.3(ATP6V0A4):c.2011-2A>T	ATP6V0A4	Likely pathogenic	criteria provided, single submitter
635428	NM_020632.3(ATP6V0A4):c.816+1G>A	ATP6V0A4	Likely pathogenic	criteria provided, single submitter
802368	NM_020632.3(ATP6V0A4):c.2451C>A (p.Phe817Leu)	ATP6V0A4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
802369	NM_020632.3(ATP6V0A4):c.1755T>A (p.Cys585Ter)	ATP6V0A4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
359004	NM_020632.3(ATP6V0A4):c.2412C>T (p.His804=)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359005	NM_020632.3(ATP6V0A4):c.2403T>C (p.Ala801=)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359009	NM_020632.3(ATP6V0A4):c.2140-9G>A	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359010	NM_020632.3(ATP6V0A4):c.1977G>A (p.Pro659=)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359016	NM_020632.3(ATP6V0A4):c.1498A>G (p.Ser500Gly)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359021	NM_020632.3(ATP6V0A4):c.1030-14T>A	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359023	NM_020632.3(ATP6V0A4):c.945C>T (p.Asp315=)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359028	NM_020632.3(ATP6V0A4):c.588C>T (p.Asn196=)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359031	NM_020632.3(ATP6V0A4):c.418-13C>G	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
359032	NM_020632.3(ATP6V0A4):c.118-3T>A	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5157	NM_020632.3(ATP6V0A4):c.1571C>T (p.Pro524Leu)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
733794	NM_020632.3(ATP6V0A4):c.1002T>C (p.Arg334=)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
745654	NM_020632.3(ATP6V0A4):c.492A>G (p.Ala164=)	ATP6V0A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 10 · 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
ATP6V1B1	Definitive	Autosomal recessive	renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss	6
ATP6V0A4	Strong	Autosomal recessive	renal tubular acidosis, distal, 3, with or without sensorineural hearing loss	4
FOXI1	Strong	Autosomal recessive	autosomal recessive distal renal tubular acidosis	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP6V0A4	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
FOXI1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
FOXI1	Orphanet:705	Pendred syndrome
ATP6V1B1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
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

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATP6V0A4	HGNC:866	ENSG00000105929	Q9HBG4	V-type proton ATPase 116 kDa subunit a 4	gencc,clinvar
FOXI1	HGNC:3815	ENSG00000168269	Q12951	Forkhead box protein I1	gencc
ATP6V1B1	HGNC:853	ENSG00000116039	P15313	V-type proton ATPase subunit B, kidney isoform	gencc
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)
ATP6V0A4	V-type proton ATPase 116 kDa subunit a 4	Subunit of the V0 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.
FOXI1	Forkhead box protein I1	Transcriptional activator required for the development of normal hearing, sense of balance and kidney function.
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.
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: 1 · Unknown: 3 · 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	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP6V0A4	Other/Unknown	no		V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka
FOXI1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
ATP6V1B1	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu
SLC4A1	Other/Unknown	no		Anion_exchange, Anion_exchange_1, HCO3_transpt_euk

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
metanephros cortex	3
adult mammalian kidney	2
renal medulla	1
olfactory segment of nasal mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
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
ATP6V0A4	150	tissue_specific	marker	metanephros cortex, adult mammalian kidney, renal medulla
FOXI1	46	tissue_specific	marker	metanephros cortex, adult mammalian kidney, olfactory segment of nasal mucosa
ATP6V1B1	152	broad	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, metanephros cortex
SLC4A1	161	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6V1B1	2,172
SLC4A1	1,598
FOXI1	1,523
ATP6V0A4	1,221

Intra-cohort edges

A	B	Sources
ATP6V0A4	ATP6V1B1	biogrid_interaction, string_interaction
ATP6V0A4	FOXI1	string_interaction
ATP6V0A4	SLC4A1	string_interaction
ATP6V1B1	FOXI1	string_interaction
ATP6V1B1	SLC4A1	string_interaction
FOXI1	SLC4A1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC4A1	P02730	54
ATP6V0A4	Q9HBG4	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP6V1B1	P15313	87.21
FOXI1	Q12951	60.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Insulin receptor recycling	2	253.8×	1e-04	ATP6V0A4, ATP6V1B1
Transferrin endocytosis and recycling	2	245.6×	1e-04	ATP6V0A4, ATP6V1B1
ROS and RNS production in phagocytes	2	223.9×	1e-04	ATP6V0A4, ATP6V1B1
Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tubular acidosis (dRTA) and dRTA with hemolytic anemia (dRTA-HA)	1	3806.7×	0.001	SLC4A1
Ion channel transport	2	64.0×	0.001	ATP6V0A4, ATP6V1B1
Erythrocytes take up oxygen and release carbon dioxide	1	423.0×	0.005	SLC4A1
O2/CO2 exchange in erythrocytes	1	423.0×	0.005	SLC4A1
Bicarbonate transporters	1	380.7×	0.005	SLC4A1
Erythrocytes take up carbon dioxide and release oxygen	1	292.8×	0.006	SLC4A1
SLC transporter disorders	1	68.0×	0.022	SLC4A1
Amino acids regulate mTORC1	1	66.8×	0.022	ATP6V1B1
Disorders of transmembrane transporters	1	46.4×	0.028	SLC4A1
R-HSA-425393	1	43.3×	0.028	SLC4A1
SLC-mediated transmembrane transport	1	19.7×	0.057	SLC4A1
Transport of small molecules	1	8.4×	0.122	SLC4A1
Disease	1	4.4×	0.212	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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
renal tubular secretion	2	2808.7×	5e-06	ATP6V0A4, ATP6V1B1
regulation of pH	2	702.2×	6e-05	ATP6V0A4, ATP6V1B1
synaptic vesicle lumen acidification	2	468.1×	9e-05	ATP6V0A4, ATP6V1B1
vacuolar acidification	2	366.4×	1e-04	ATP6V0A4, ATP6V1B1
proton transmembrane transport	2	156.0×	5e-04	ATP6V0A4, ATP6V1B1
inner ear morphogenesis	2	150.5×	5e-04	FOXI1, ATP6V1B1
ossification	2	113.9×	7e-04	ATP6V0A4, ATP6V1B1
response to increased oxygen levels	1	4213.0×	0.001	SLC4A1
pH elevation	1	4213.0×	0.001	SLC4A1
sensory perception of sound	2	50.5×	0.002	ATP6V0A4, ATP6V1B1
renal sodium ion transport	1	1053.2×	0.003	ATP6V1B1
intracellular monoatomic ion homeostasis	1	1053.2×	0.003	SLC4A1
negative regulation of urine volume	1	1053.2×	0.003	SLC4A1
renal sodium excretion	1	1053.2×	0.003	ATP6V1B1
vacuolar proton-transporting V-type ATPase complex assembly	1	702.2×	0.004	ATP6V1B1
negative regulation of glycolytic process through fructose-6-phosphate	1	702.2×	0.004	SLC4A1
pH reduction	1	601.9×	0.004	ATP6V1B1
olfactory behavior	1	468.1×	0.005	ATP6V1B1
plasma membrane phospholipid scrambling	1	383.0×	0.006	SLC4A1
chloride ion homeostasis	1	383.0×	0.006	ATP6V1B1
monoatomic anion transport	1	351.1×	0.006	SLC4A1
intracellular pH reduction	1	300.9×	0.006	ATP6V0A4
prostaglandin metabolic process	1	210.7×	0.009	ATP6V1B1
bicarbonate transport	1	200.6×	0.009	SLC4A1
potassium ion homeostasis	1	191.5×	0.009	ATP6V1B1
embryo development ending in birth or egg hatching	1	183.2×	0.009	FOXI1
regulation of intracellular pH	1	150.5×	0.011	SLC4A1
erythrocyte development	1	131.7×	0.012	SLC4A1
renal water homeostasis	1	127.7×	0.012	ATP6V1B1
adult behavior	1	117.0×	0.012	ATP6V1B1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP6V0A4	0	0
FOXI1	0	0
ATP6V1B1	0	0
SLC4A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP6V1B1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	ATP6V0A4, FOXI1, ATP6V1B1, SLC4A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ATP6V0A4	0	—
FOXI1	0	—
ATP6V1B1	1	—
SLC4A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases