SLC4A10

Summary

SLC4A10 (solute carrier family 4 member 10, HGNC:13811) is a protein-coding gene on chromosome 2q24.2, encoding Sodium-driven chloride bicarbonate exchanger (Q6U841). Sodium/bicarbonate cotransporter which plays an important role in regulating intracellular pH.

This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 57282 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 22
• Clinical variants (ClinVar): 156 total — 7 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001178015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13811
Approved symbol	SLC4A10
Name	solute carrier family 4 member 10
Location	2q24.2
Locus type	gene with protein product
Status	Approved
Aliases	NBCn2, NCBE
Ensembl gene	ENSG00000144290
Ensembl biotype	protein_coding
OMIM	605556
Entrez	57282

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000272716, ENST00000375514, ENST00000415876, ENST00000421911, ENST00000446228, ENST00000446997, ENST00000461456, ENST00000481721, ENST00000482861, ENST00000493021, ENST00000605990, ENST00000606386, ENST00000947395

RefSeq mRNA: 19 — MANE Select: NM_001178015 NM_001178015, NM_001178016, NM_001354440, NM_001354441, NM_001354442, NM_001354443, NM_001354444, NM_001354445, NM_001354446, NM_001354447, NM_001354448, NM_001354449, NM_001354450, NM_001354451, NM_001354453, NM_001354455, NM_001354460, NM_001354461, NM_022058

CCDS: CCDS46438, CCDS54411, CCDS54412, CCDS86888

Canonical transcript exons

ENST00000446997 — 27 exons

Exon	Start	End
ENSE00001711525	161983179	161985270
ENSE00003469978	161905642	161905887
ENSE00003476720	161965051	161965173
ENSE00003476966	161873916	161874005
ENSE00003478297	161942792	161942897
ENSE00003478617	161977722	161977760
ENSE00003485574	161879131	161879288
ENSE00003485990	161804449	161804595
ENSE00003487312	161974249	161974316
ENSE00003491350	161976760	161976876
ENSE00003508986	161894679	161894825
ENSE00003530489	161949148	161949261
ENSE00003554829	161872293	161872384
ENSE00003556787	161770973	161771054
ENSE00003556928	161839789	161839927
ENSE00003567310	161882357	161882444
ENSE00003567964	161956989	161957240
ENSE00003578031	161964135	161964308
ENSE00003587984	161900911	161901011
ENSE00003609438	161947566	161947727
ENSE00003631254	161950687	161950848
ENSE00003645195	161904776	161904909
ENSE00003650814	161958487	161958555
ENSE00003655875	161862874	161863062
ENSE00003663492	161904004	161904178
ENSE00003667918	161854970	161855130
ENSE00003848134	161624416	161624566

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 95.72.

FANTOM5 (CAGE): breadth broad, TPM avg 10.3906 / max 4349.1451, expressed in 300 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23347	7.3312	263
23348	1.2744	155
23346	0.9098	126
23345	0.3600	93
23349	0.2047	70
23350	0.1002	45
23340	0.0788	29
23341	0.0459	16
23342	0.0343	19
23344	0.0304	15

Top tissues by expression

118 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	95.72	gold quality
prefrontal cortex	UBERON:0000451	92.16	gold quality
primary visual cortex	UBERON:0002436	91.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.49	gold quality
frontal cortex	UBERON:0001870	90.12	gold quality
frontal lobe	UBERON:0016525	90.12	gold quality
corpus callosum	UBERON:0002336	89.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.61	gold quality
cerebral cortex	UBERON:0000956	87.96	gold quality
islet of Langerhans	UBERON:0000006	86.96	gold quality
cortical plate	UBERON:0005343	86.65	gold quality
anterior cingulate cortex	UBERON:0009835	86.48	gold quality
right frontal lobe	UBERON:0002810	86.29	gold quality
cerebellar cortex	UBERON:0002129	84.13	gold quality
cerebellum	UBERON:0002037	84.12	gold quality
cerebellar hemisphere	UBERON:0002245	84.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.60	gold quality
brain	UBERON:0000955	81.41	gold quality
nucleus accumbens	UBERON:0001882	81.05	gold quality
ganglionic eminence	UBERON:0004023	80.59	gold quality
Ammon’s horn	UBERON:0001954	80.53	gold quality
hypothalamus	UBERON:0001898	80.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.21	silver quality
temporal lobe	UBERON:0001871	78.36	gold quality
amygdala	UBERON:0001876	78.15	gold quality
ventricular zone	UBERON:0003053	76.10	gold quality
caudate nucleus	UBERON:0001873	76.07	gold quality
putamen	UBERON:0001874	73.99	gold quality
mucosa of transverse colon	UBERON:0004991	70.92	gold quality
substantia nigra	UBERON:0002038	70.68	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	249.76
E-HCAD-35	yes	91.41
E-HCAD-25	yes	80.71
E-MTAB-7316	yes	33.06
E-ANND-3	yes	5.85
E-MTAB-6678	yes	4.82
E-GEOD-70580	no	498.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting SLC4A10, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 6)

• propose to rename NCBE as the second electroneutral Na/HCO(3) cotransporter, NBCn2 (PMID:18319254)
• SLC4A10 (OMIM 605556), a sodium bicarbonate transporter gene with high expression in the cerebral cortex and hippocampus, was disrupted by the translocation breakpoint on chromosome 2q24. (PMID:18413482)
• There was no association between common sequence variants in the AQP1 or SLC4A10 genes and primary open-angle glaucoma in the Caucasian population. (PMID:20101282)
• genetic variation in SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance (PMID:28360221)
• SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission. (PMID:37459438)
• Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder. (PMID:38054405)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc4a10b	ENSDARG00000060303
danio_rerio	slc4a10a	ENSDARG00000063133
mus_musculus	Slc4a10	ENSMUSG00000026904
rattus_norvegicus	Slc4a10	ENSRNOG00000005307
drosophila_melanogaster	Ae2	FBGN0036043
drosophila_melanogaster	Ndae1	FBGN0259111
caenorhabditis_elegans	abts-1	WBGENE00009920
caenorhabditis_elegans		WBGENE00019844

Paralogs (9): SLC4A1 (ENSG00000004939), SLC4A7 (ENSG00000033867), SLC4A8 (ENSG00000050438), SLC4A4 (ENSG00000080493), SLC4A11 (ENSG00000088836), SLC4A9 (ENSG00000113073), SLC4A3 (ENSG00000114923), SLC4A2 (ENSG00000164889), SLC4A5 (ENSG00000188687)

Protein

Protein identifiers

Sodium-driven chloride bicarbonate exchanger — Q6U841 (reviewed: Q6U841)

Alternative names: Solute carrier family 4 member 10

All UniProt accessions (4): Q6U841, C9J240, E7EW28, F8WDX9

UniProt curated annotations — full annotation on UniProt →

Function. Sodium/bicarbonate cotransporter which plays an important role in regulating intracellular pH. Has been shown to act as a sodium/bicarbonate cotransporter in exchange for intracellular chloride. Has also been shown to act as a sodium/biocarbonate cotransporter which does not couple net influx of bicarbonate to net efflux of chloride, with the observed chloride efflux being due to chloride self-exchange. Controls neuronal pH and may contribute to the secretion of cerebrospinal fluid. Acting on presynaptic intracellular pH, it promotes GABA release, reduces the excitability of CA1 pyramidal neurons, and modulates short-term synaptic plasticity. Required in retinal cells to maintain normal pH which is necessary for normal vision. In the kidney, likely to mediate bicarbonate reclamation in the apical membrane of the proximal tubules.

Subcellular location. Basolateral cell membrane. Apical cell membrane. Cell projection. Dendrite. Axon. Perikaryon. Presynapse. Postsynapse.

Tissue specificity. Predominantly expressed in the brain.

Disease relevance. Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities (NEDHBA) [MIM:620746] An autosomal recessive disorder characterized by hypotonia in infancy, delayed psychomotor development and intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorder including anxiety, hyperactivity and stereotyped movements. Episodes of seizures in the first few years of life may occur. Brain imaging shows abnormalities of the lateral ventricles. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal cytoplasmic domain is likely to have a high level of intrinsic disorder.

Similarity. Belongs to the anion exchanger (TC 2.A.31) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6U841-1	1, NCBE-B	yes
Q6U841-2	2, NCBE-A
Q6U841-3	3
Q6U841-4	4

RefSeq proteins (19): NP_001171486, NP_001171487, NP_001341369, NP_001341370, NP_001341371, NP_001341372, NP_001341373, NP_001341374, NP_001341375, NP_001341376, NP_001341377, NP_001341378, NP_001341379, NP_001341380, NP_001341382, NP_001341384, NP_001341389, NP_001341390, NP_071341 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003020	HCO3_transpt_euk	Family
IPR003024	Na/HCO3_transpt	Family
IPR011531	HCO3_transpt-like_TM_dom	Domain
IPR013769	Band3_cytoplasmic_dom	Domain
IPR016152	PTrfase/Anion_transptr	Homologous_superfamily

Pfam: PF00955, PF07565

Catalyzed reactions (Rhea), 1 shown:

• 2 hydrogencarbonate(out) + chloride(in) + Na(+)(out) = 2 hydrogencarbonate(in) + chloride(out) + Na(+)(in) (RHEA:72739)

UniProt features (70 total): topological domain 13, transmembrane region 12, sequence variant 11, sequence conflict 10, modified residue 5, region of interest 4, glycosylation site 4, splice variant 4, compositionally biased region 3, mutagenesis site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6U841-F1	71.37	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 89, 94, 276, 1057, 1085

Glycosylation sites (4): 674, 677, 687, 697

Mutagenesis-validated functional residues (3):

Position	Phenotype
677	reduced glycosylation. abolishes glycosylation; when associated with q-687 and q-697.
687	reduced glycosylation. abolishes glycosylation; when associated with q-677 and q-697.
697	reduced glycosylation. abolishes glycosylation; when associated with q-677 and q-687.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-425381	Bicarbonate transporters
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 353 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, RNGTGGGC_UNKNOWN, TAATAAT_MIR126, GOBP_BEHAVIOR, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_GROWTH, GOBP_REGULATION_OF_SHORT_TERM_NEURONAL_SYNAPTIC_PLASTICITY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_NEUROGENESIS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_FOREBRAIN_GENERATION_OF_NEURONS

GO Biological Process (23): chloride transport (GO:0006821), visual perception (GO:0007601), response to light stimulus (GO:0009416), post-embryonic development (GO:0009791), bicarbonate transport (GO:0015701), pyramidal neuron development (GO:0021860), multicellular organism growth (GO:0035264), locomotory exploration behavior (GO:0035641), regulation of short-term neuronal synaptic plasticity (GO:0048172), brain morphogenesis (GO:0048854), regulation of intracellular pH (GO:0051453), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), monoatomic anion transport (GO:0006820), regulation of pH (GO:0006885), inorganic anion transport (GO:0015698), obsolete regulation of cellular pH (GO:0030641), monoatomic ion transmembrane transport (GO:0034220), sodium ion transmembrane transport (GO:0035725), monoatomic anion transmembrane transport (GO:0098656), obsolete inorganic ion transmembrane transport (GO:0098660)

GO Molecular Function (9): solute:inorganic anion antiporter activity (GO:0005452), sodium:bicarbonate symporter activity (GO:0008510), sodium,bicarbonate:chloride antiporter activity (GO:0140892), monoatomic anion transmembrane transporter activity (GO:0008509), monoatomic ion transmembrane transporter activity (GO:0015075), bicarbonate transmembrane transporter activity (GO:0015106), secondary active transmembrane transporter activity (GO:0015291), symporter activity (GO:0015293), antiporter activity (GO:0015297)

GO Cellular Component (18): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), dendrite (GO:0030425), somatodendritic compartment (GO:0036477), neuronal cell body (GO:0043025), perikaryon (GO:0043204), axon terminus (GO:0043679), synapse (GO:0045202), apical dendrite (GO:0097440), basal dendrite (GO:0097441), CA3 pyramidal cell dendrite (GO:0097442), postsynapse (GO:0098794), GABA-ergic synapse (GO:0098982), axon (GO:0030424), cell projection (GO:0042995), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
transport	4
dendrite	3
synapse	3
multicellular organismal process	2
monoatomic ion transport	2
transmembrane transporter activity	2
secondary active transmembrane transporter activity	2
plasma membrane region	2
neuron projection	2
monoatomic anion transport	1
inorganic anion transport	1
sensory perception of light stimulus	1
response to radiation	1
multicellular organism development	1
pyramidal neuron differentiation	1
forebrain neuron development	1
developmental growth	1
locomotory behavior	1
exploration behavior	1
regulation of neuronal synaptic plasticity	1
brain development	1
animal organ morphogenesis	1
regulation of pH	1
intracellular monoatomic cation homeostasis	1
regulation of biological quality	1
cellular process	1
monoatomic cation transmembrane transport	1
metal ion transport	1
monoatomic cation homeostasis	1
biological regulation	1
transmembrane transport	1
antiporter activity	1
solute:sodium symporter activity	1
monoatomic cation:bicarbonate symporter activity	1
sodium ion transmembrane transporter activity	1
metal cation:monoatomic cation antiporter activity	1
chloride:bicarbonate antiporter activity	1
monoatomic ion transmembrane transporter activity	1
monoatomic anion transmembrane transport	1

Protein interactions and networks

STRING

1528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC4A10	AHCYL1	O43865	636
SLC4A10	SLC12A2	P55011	571
SLC4A10	SLC9A1	P19634	546
SLC4A10	KCNH7	Q9NS40	517
SLC4A10	TMEM235	A6NFC5	491
SLC4A10	SLC26A6	Q9BXS9	485
SLC4A10	SLC9A3	P48764	475
SLC4A10	SLC9A2	Q9UBY0	464
SLC4A10	SLC9A5	Q14940	464
SLC4A10	AQP1	P29972	463
SLC4A10	SLC26A4	O43511	454
SLC4A10	SLC26A9	Q7LBE3	440
SLC4A10	PRRT2	Q7Z6L0	440
SLC4A10	SV2B	Q7L1I2	429
SLC4A10	SLC9A4	Q6AI14	423

IntAct

10 interactions, top by confidence:

A	B	Type	Score
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC4A10	RER1	psi-mi:“MI:0914”(association)	0.350
SLC4A8	PSMA7	psi-mi:“MI:0914”(association)	0.350
FOS	SLC4A10	psi-mi:“MI:0915”(physical association)	0.000
SLC4A10	CBFB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): SLC4A10 (Affinity Capture-MS), SLC4A10 (Affinity Capture-MS), SLC4A10 (Affinity Capture-MS), SLC4A10 (Affinity Capture-MS), SLC4A10 (Affinity Capture-MS), SLC4A10 (Affinity Capture-MS), SLC4A10 (Co-fractionation), SLC4A7 (Co-fractionation), SLC4A10 (Co-fractionation), SLC4A10 (Co-fractionation), SLMAP (Co-fractionation), TXK (Co-fractionation), ARV1 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), CANX (Affinity Capture-MS)

ESM2 similar proteins: A0A096X8J7, B1MTL0, E9Q3M5, G3X939, M5A7P9, O13134, O18917, O88343, P04919, P13808, P16283, P19334, P23347, P23348, P23562, P23685, P26433, P32418, P32847, P34586, P48746, P48751, P48765, P48766, P48767, P48994, P70414, P90895, Q01728, Q28362, Q2Y0W8, Q32LP4, Q4U116, Q5DTL9, Q5RB85, Q5RD44, Q6RI88, Q6RVG2, Q6SJP2, Q6U841

Diamond homologs: A0A096X8J7, A0A494BA31, B1MTL0, E9Q3M5, O13134, O18917, O88343, P02730, P04919, P04920, P13808, P15575, P16283, P23347, P23348, P23562, P32847, P48746, P48751, Q2Y0W8, Q32LP4, Q4U116, Q5DTL9, Q5RB85, Q5RD44, Q6RI88, Q6RVG2, Q6SJP2, Q6U841, Q80ZA5, Q8BTY2, Q8JZR6, Q8K4V2, Q96Q91, Q9BY07, Q9GKY1, Q9GL77, Q9JI66, Q9R1N3, Q9XSZ4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SLC4A10	“down-regulates quantity”	chloride	relocalization
SLC4A10	“up-regulates quantity”	hydrogencarbonate	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

156 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	5
Uncertain significance	116
Likely benign	14
Benign	5

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
3027499	NM_001178015.2(SLC4A10):c.417-1341del	Pathogenic
3027504	NM_001178015.2(SLC4A10):c.2894C>T (p.Pro965Leu)	Pathogenic
3027505	NM_001178015.2(SLC4A10):c.1052G>C (p.Arg351Thr)	Pathogenic
3027506	NM_001178015.2(SLC4A10):c.1864C>T (p.Arg622Trp)	Pathogenic
3027507	NM_001178015.2(SLC4A10):c.2162A>G (p.Tyr721Cys)	Pathogenic
3027508	NM_001178015.2(SLC4A10):c.667C>T (p.His223Tyr)	Pathogenic
4292590	NM_001178015.2(SLC4A10):c.2184G>A (p.Trp728Ter)	Pathogenic
1342970	Single allele	Likely pathogenic
1342973	NM_001178015.2(SLC4A10):c.2619G>A (p.Trp873Ter)	Likely pathogenic
2574737	NM_001178015.2(SLC4A10):c.858+1G>C	Likely pathogenic
3393295	NM_001178015.2(SLC4A10):c.3160-2_3160-1insC	Likely pathogenic
4682465	NM_001178015.2(SLC4A10):c.874del (p.Gln292fs)	Likely pathogenic

SpliceAI

3890 predictions. Top by Δscore:

Variant	Effect	Δscore
2:161624563:TACGG:T	donor_loss	1.0000
2:161624564:ACGGT:A	donor_loss	1.0000
2:161624566:GGT:G	donor_loss	1.0000
2:161624567:GT:G	donor_loss	1.0000
2:161624568:T:G	donor_loss	1.0000
2:161770964:A:AG	acceptor_gain	1.0000
2:161770971:A:AC	acceptor_loss	1.0000
2:161770971:A:AG	acceptor_gain	1.0000
2:161770972:G:GA	acceptor_gain	1.0000
2:161770972:G:GT	acceptor_loss	1.0000
2:161770972:GA:G	acceptor_gain	1.0000
2:161770972:GAGA:G	acceptor_gain	1.0000
2:161770972:GAGAA:G	acceptor_gain	1.0000
2:161771052:AAGGT:A	donor_loss	1.0000
2:161771053:AGG:A	donor_loss	1.0000
2:161771055:GTAAG:G	donor_loss	1.0000
2:161771056:T:G	donor_loss	1.0000
2:161804444:T:G	acceptor_gain	1.0000
2:161804444:T:TA	acceptor_gain	1.0000
2:161804593:TTGG:T	donor_loss	1.0000
2:161804595:GGT:G	donor_loss	1.0000
2:161804596:GTAA:G	donor_loss	1.0000
2:161804597:T:A	donor_loss	1.0000
2:161839785:TTA:T	acceptor_loss	1.0000
2:161839787:A:AG	acceptor_gain	1.0000
2:161839788:G:GG	acceptor_gain	1.0000
2:161839788:GA:G	acceptor_gain	1.0000
2:161839788:GACA:G	acceptor_gain	1.0000
2:161839788:GACAC:G	acceptor_gain	1.0000
2:161839923:GCCAG:G	donor_gain	1.0000

AlphaMissense

7365 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:161839873:T:C	L121P	1.000
2:161839911:T:A	W134R	1.000
2:161839911:T:C	W134R	1.000
2:161839913:G:C	W134C	1.000
2:161839913:G:T	W134C	1.000
2:161839927:G:C	R139T	1.000
2:161839927:G:T	R139M	1.000
2:161854970:G:C	R139S	1.000
2:161854970:G:T	R139S	1.000
2:161854971:T:A	W140R	1.000
2:161854971:T:C	W140R	1.000
2:161854973:G:C	W140C	1.000
2:161854973:G:T	W140C	1.000
2:161854975:T:C	L141S	1.000
2:161854980:T:A	F143I	1.000
2:161854980:T:C	F143L	1.000
2:161854981:T:C	F143S	1.000
2:161854981:T:G	F143C	1.000
2:161854982:T:A	F143L	1.000
2:161854982:T:G	F143L	1.000
2:161854985:A:C	E144D	1.000
2:161854985:A:T	E144D	1.000
2:161855011:G:T	R153M	1.000
2:161855012:G:C	R153S	1.000
2:161855012:G:T	R153S	1.000
2:161855013:T:A	W154R	1.000
2:161855013:T:C	W154R	1.000
2:161855014:G:C	W154S	1.000
2:161855015:G:C	W154C	1.000
2:161855015:G:T	W154C	1.000

dbSNP variants (sampled 300 via entrez): RS1000001203 (2:161920053 C>A), RS1000008697 (2:161758496 T>G), RS1000013496 (2:161935657 G>A), RS1000018266 (2:161808920 G>A,C), RS1000021725 (2:161933733 G>A), RS1000045383 (2:161666357 A>T), RS1000048092 (2:161984735 A>T), RS1000050170 (2:161802364 G>T), RS1000058664 (2:161812187 G>C,T), RS1000060379 (2:161902534 T>G), RS1000062606 (2:161758225 T>C), RS1000072849 (2:161639744 T>G), RS1000073176 (2:161970065 A>G,T), RS1000092195 (2:161899948 A>T), RS1000098950 (2:161693128 T>G)

Disease associations

OMIM: gene MIM:605556 | disease phenotypes: MIM:620746

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with hypotonia and characteristic brain abnormalities	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	AR

Mondo (1): neurodevelopmental disorder with hypotonia and characteristic brain abnormalities (MONDO:0958278)

Orphanet (1): Neurodevelopmental disorder-slit-like lateral ventricles-intellectual disability syndrome (Orphanet:664430)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000303	Mandibular prognathia
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000505	Visual impairment
HP:0000527	Long eyelashes
HP:0000601	Hypotelorism
HP:0000664	Synophrys
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000752	Hyperactivity
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST002539_38	Schizophrenia	5.000000e-08
GCST003469_8	Response to cognitive-behavioural therapy in anxiety disorder	8.000000e-06
GCST004001_10	Bipolar disorder or attention deficit hyperactivity disorder	9.000000e-07
GCST004267_2	Blood osmolality (transformed sodium)	7.000000e-08
GCST005316_163	Intelligence (MTAG)	5.000000e-17
GCST006032_3	Sodium levels	2.000000e-11
GCST006269_1080	General cognitive ability	3.000000e-11
GCST006628_29	Systolic blood pressure	1.000000e-10
GCST006803_53	Schizophrenia	4.000000e-07
GCST006870_1	Hippocampal tail volume	9.000000e-22
GCST006871_7	Total hippocampal volume	5.000000e-13
GCST006881_1	Hippocampal tail volume (corrected for total hippocampal volume)	3.000000e-13
GCST006886_2	Subiculum volume	6.000000e-11
GCST006891_1	Dentate gyrus molecular layer volume	2.000000e-10
GCST006921_12	Regular attendance at a pub or social club	2.000000e-08
GCST007277_3	Tourette syndrome	2.000000e-07
GCST007603_32	Smoking initiation	1.000000e-11
GCST008163_148	Height	8.000000e-06
GCST008595_57	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-13
GCST011494_14	Daytime nap	7.000000e-10
GCST011703_55	Smoking initiation	1.000000e-12
GCST011773_25	Type 1 diabetes (age at diagnosis)	2.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0004337	intelligence
EFO:0009282	sodium measurement
EFO:0006335	systolic blood pressure
EFO:0005035	hippocampal volume
EFO:0009592	social interaction measurement
EFO:0005670	smoking initiation
EFO:0004784	self reported educational attainment
EFO:0007828	daytime rest measurement
EFO:0004918	age at diagnosis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Sodium-dependent HCO₃^- transporters

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fluorene-9-bisphenol	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	decreases expression	1
CGP 52608	increases reaction, affects binding	1
gardiquimod	decreases reaction, increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Manganese	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TN87	HAP1 SLC4A10 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.