CHP1

Summary

CHP1 (calcineurin like EF-hand protein 1, HGNC:17433) is a protein-coding gene on chromosome 15q15.1, encoding Calcineurin B homologous protein 1 (Q99653). Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription.

This gene encodes a phosphoprotein that binds to the Na+/H+ exchanger NHE1. This protein serves as an essential cofactor which supports the physiological activity of NHE family members and may play a role in the mitogenic regulation of NHE1. The protein shares similarity with calcineurin B and calmodulin and it is also known to be an endogenous inhibitor of calcineurin activity.

Source: NCBI Gene 11261 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic ataxia 9, autosomal recessive (Limited, GenCC)
• Clinical variants (ClinVar): 12 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_007236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17433
Approved symbol	CHP1
Name	calcineurin like EF-hand protein 1
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	Sid470p, CHP, SLC9A1BP, p22, p24
Ensembl gene	ENSG00000187446
Ensembl biotype	protein_coding
OMIM	606988
Entrez	11261

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000334660, ENST00000392151, ENST00000558351, ENST00000560397, ENST00000560411, ENST00000560633, ENST00000560784, ENST00000560965, ENST00000561280, ENST00000854963, ENST00000854964, ENST00000854965, ENST00000927240

RefSeq mRNA: 1 — MANE Select: NM_007236 NM_007236

CCDS: CCDS10073

Canonical transcript exons

ENST00000334660 — 7 exons

Exon	Start	End
ENSE00001349277	41279336	41281887
ENSE00002551561	41231268	41231449
ENSE00003503297	41256910	41256990
ENSE00003506832	41262756	41262883
ENSE00003508770	41278767	41278889
ENSE00003535284	41243667	41243739
ENSE00003624756	41270557	41270618

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 115.0623 / max 1009.6257, expressed in 1827 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146161	103.1522	1825
146160	7.1369	1665
146162	2.8943	1304
146170	0.7814	461
146159	0.3972	219
146171	0.3167	128
146167	0.1601	47
146163	0.1199	28
146164	0.0470	13
146165	0.0366	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	98.71	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.63	gold quality
jejunal mucosa	UBERON:0000399	98.47	gold quality
esophagus squamous epithelium	UBERON:0006920	98.36	gold quality
mammalian vulva	UBERON:0000997	98.28	gold quality
epithelium of esophagus	UBERON:0001976	98.22	gold quality
mucosa of transverse colon	UBERON:0004991	98.19	gold quality
nasal cavity epithelium	UBERON:0005384	98.15	gold quality
ileal mucosa	UBERON:0000331	98.04	gold quality
duodenum	UBERON:0002114	98.02	gold quality
pharyngeal mucosa	UBERON:0000355	97.99	gold quality
gingiva	UBERON:0001828	97.86	gold quality
upper leg skin	UBERON:0004262	97.83	gold quality
pons	UBERON:0000988	97.75	gold quality
oral cavity	UBERON:0000167	97.70	gold quality
body of tongue	UBERON:0011876	97.61	gold quality
gingival epithelium	UBERON:0001949	97.59	gold quality
palpebral conjunctiva	UBERON:0001812	97.38	gold quality
pylorus	UBERON:0001166	97.37	gold quality
type B pancreatic cell	CL:0000169	97.26	gold quality
liver	UBERON:0002107	97.25	gold quality
skin of hip	UBERON:0001554	97.23	gold quality
squamous epithelium	UBERON:0006914	97.19	gold quality
rectum	UBERON:0001052	97.18	gold quality
amniotic fluid	UBERON:0000173	97.15	gold quality
colonic epithelium	UBERON:0000397	97.13	gold quality
penis	UBERON:0000989	97.13	gold quality
jejunum	UBERON:0002115	97.05	gold quality
tongue	UBERON:0001723	96.86	gold quality
adult organism	UBERON:0007023	96.77	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	25.33
E-GEOD-86618	no	1957.30
E-MTAB-6379	no	828.26
E-GEOD-106540	no	622.28
E-MTAB-7052	no	344.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

185 targeting CHP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-145-5P	99.92	71.13	1836

Literature-anchored findings (GeneRIF, showing 10)

• serum-independent activation of NHE1 by bound CHP2 is one of the key mechanisms for the maintenance of high pH(i) and the resistance to serum deprivation-induced cell death in malignantly transformed cells (PMID:12226101)
• CHP is important for pH(i)-dependent regulation of Na+/H+ exchanger 1 (NHE1) via tightly bound Ca2+ ions which serve as a crucial structural elements required for this role. (PMID:15035633)
• crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1 (PMID:16511206)
• helix formation of the cytoplasmic region of NHE1 by calcineurin B homologous protein 1 is a prerequisite for generating the active form of NHE1 (PMID:17050540)
• CHP2 has a role in tumorigenesis and as an activator of the calcineurin/NFAT signaling pathway (PMID:18815128)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• GPAT4 activity requires CHP1 to be N-myristoylated, forming a key molecular interface between the two proteins, regulating glycerolipid metabolism. (PMID:30846317)
• Novel CHP1 mutation in autosomal-recessive cerebellar ataxia: autopsy features of two siblings. (PMID:32787936)
• Structure and mechanism of the human NHE1-CHP1 complex. (PMID:34108458)
• Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis. (PMID:38360885)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	chp2	ENSDARG00000025788
mus_musculus	Chp1	ENSMUSG00000014077
rattus_norvegicus	Chp1	ENSRNOG00000004742
rattus_norvegicus	LOC120102456	ENSRNOG00000062492
drosophila_melanogaster	CG32812	FBGN0025642
drosophila_melanogaster	Cib2	FBGN0034558
drosophila_melanogaster	elm	FBGN0037358
drosophila_melanogaster	CG14362	FBGN0038186
caenorhabditis_elegans	calm-1	WBGENE00009260
caenorhabditis_elegans		WBGENE00014109
caenorhabditis_elegans		WBGENE00019108

Paralogs (8): TESC (ENSG00000088992), CIB2 (ENSG00000136425), CIB3 (ENSG00000141977), CIB4 (ENSG00000157884), CHP2 (ENSG00000166869), CIB1 (ENSG00000185043), PPP3R2 (ENSG00000188386), PPP3R1 (ENSG00000221823)

Protein

Protein identifiers

Calcineurin B homologous protein 1 — Q99653 (reviewed: Q99653)

Alternative names: Calcineurin B-like protein, Calcium-binding protein CHP, Calcium-binding protein p22, EF-hand calcium-binding domain-containing protein p22

All UniProt accessions (6): F5GX29, Q99653, H0YKE7, H0YLX1, H0YLY7, H0YNG9

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membrane. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium-dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate-phosphorylations in a calcium-dependent manner.

Subunit / interactions. Monomer. Interacts with STK17B; the interaction occurs in a calcium-independent manner and induces the translocation of CHP1 from the Golgi to the nucleus. Interacts with GAPDH; the interaction is direct, occurs in a N-myristoylation-dependent manner and facilitates the ability of CHP1 to bind microtubules. Interacts with KIF1B (via the C-terminal end of the kinesin-motor domain); the interaction occurs in a calcium-dependent manner. Associates (via C-terminal domain) with microtubules; the association occurs with polymerized microtubules during the cell cycle in a myristoylation- and calcium-independent manner and is enhanced by GAPDH. Interacts with PPP3CA. Interacts with SLC9A1/NHE1 (via the C-terminal domain); the interaction occurs at the plasma membrane in a calcium-dependent manner and at a domain that is critical for growth factor stimulation of the exchanger. Interacts with SLC9A3; increases SLC9A3 trafficking and activity at the plasma membrane.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Endomembrane system. Endoplasmic reticulum-Golgi intermediate compartment. Endoplasmic reticulum. Cell membrane. Membrane.

Tissue specificity. Ubiquitously expressed. Has been found in fetal eye, lung, liver, muscle, heart, kidney, thymus and spleen.

Post-translational modifications. Phosphorylated; decreased phosphorylation is associated with an increase in SLC9A1/NHE1 Na(+)/H(+) exchange activity. Phosphorylation occurs in serum-dependent manner. The phosphorylation state may regulate the binding to SLC9A1/NHE1. Both N-myristoylation and calcium-mediated conformational changes are essential for its function in exocytic traffic. N-myristoylation is required for its association with microtubules and interaction with GAPDH, but not for the constitutive association to membranes.

Disease relevance. Spastic ataxia 9, autosomal recessive (SPAX9) [MIM:618438] An autosomal recessive disorder characterized by onset of spastic ataxia in the first years of life. Clinical features include motor neuropathy, cerebellar atrophy, spastic paraparesis, intellectual disability, slow ocular saccades, axial hypotonia, distal muscle weakness and atrophy, and pyramidal symptoms, including hyperreflexia and extensor plantar responses. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the calcineurin regulatory subunit family. CHP subfamily.

RefSeq proteins (1): NP_009167* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR051875	Calcineurin_B_homologous	Family

Pfam: PF13499

UniProt features (52 total): helix 13, binding site 9, mutagenesis site 9, strand 8, domain 4, short sequence motif 3, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence variant 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7X2U	ELECTRON MICROSCOPY	3.2
7DSV	ELECTRON MICROSCOPY	3.4
7DSX	ELECTRON MICROSCOPY	3.5
2E30	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99653-F1	89.45	0.74

Functional residue map

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

Ligand- & substrate-binding residues (9): 123; 125; 127; 129; 134; 164; 166; 168; 175

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (9):

Position	Phenotype
50	does not reduce calcium-binding, colocalization and interaction with slc9a1.
134	reduces calcium-binding and slc9a1-dependent na(+)/h(+) exchange activity. does not reduce colocalization and interactio
143	inhibits translocation to the cytoplasm; when associated with a-145; a-147; a-183 and a-185.
145	inhibits translocation to the cytoplasm; when associated with a-143; a-147; a-183 and a-185.
147	inhibits translocation to the cytoplasm; when associated with a-143; a-145; a-183 and a-185.
175	reduces calcium-binding and slc9a1-dependent na(+)/h(+) exchange activity. does not reduce colocalization and interactio
183	inhibits translocation to the cytoplasm; when associated with a-143; a-145; a-147 and a-185.
185	inhibits translocation to the cytoplasm; when associated with a-143; a-145; a-147 and a-183.
192	does not affect sodium:proton antiporter activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2160916	Hyaluronan degradation

MSigDB gene sets: 462 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, AP1_01, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_PHOSPHATASE_ACTIVITY, LFA1_Q6, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP

GO Biological Process (29): microtubule bundle formation (GO:0001578), negative regulation of protein phosphorylation (GO:0001933), negative regulation of protein kinase activity (GO:0006469), protein export from nucleus (GO:0006611), potassium ion transport (GO:0006813), small GTPase-mediated signal transduction (GO:0007264), positive regulation of glycoprotein biosynthetic process (GO:0010560), negative regulation of phosphatase activity (GO:0010923), membrane docking (GO:0022406), cytoplasmic microtubule organization (GO:0031122), negative regulation of protein ubiquitination (GO:0031397), negative regulation of protein autophosphorylation (GO:0031953), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), positive regulation of sodium:proton antiporter activity (GO:0032417), negative regulation of protein import into nucleus (GO:0042308), protein stabilization (GO:0050821), positive regulation of protein transport (GO:0051222), regulation of intracellular pH (GO:0051453), membrane organization (GO:0061024), membrane fusion (GO:0061025), negative regulation of calcineurin-NFAT signaling cascade (GO:0070885), positive regulation of phospholipid biosynthetic process (GO:0071073), cellular response to acidic pH (GO:0071468), positive regulation of protein targeting to membrane (GO:0090314), protein transport (GO:0015031), sodium ion transmembrane transport (GO:0035725), regulation of protein import into nucleus (GO:0042306), obsolete positive regulation of protein glycosylation (GO:0060050), regulation of calcineurin-NFAT signaling cascade (GO:0070884)

GO Molecular Function (9): protein kinase inhibitor activity (GO:0004860), calcium ion binding (GO:0005509), microtubule binding (GO:0008017), sodium:proton antiporter activity (GO:0015385), potassium channel regulator activity (GO:0015459), kinase binding (GO:0019900), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (15): Golgi membrane (GO:0000139), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), plasma membrane (GO:0005886), focal adhesion (GO:0005925), microtubule cytoskeleton (GO:0015630), transport vesicle (GO:0030133), membrane raft (GO:0045121), extracellular exosome (GO:0070062), transporter complex (GO:1990351), cytoskeleton (GO:0005856), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hyaluronan metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
microtubule cytoskeleton organization	2
negative regulation of protein phosphorylation	2
protein kinase activity	2
cytoplasm	2
endomembrane system	2
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
intracellular protein transport	1
nuclear export	1
metal ion transport	1
intracellular signaling cassette	1
glycoprotein biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
regulation of glycoprotein biosynthetic process	1
positive regulation of glycoprotein metabolic process	1
regulation of phosphatase activity	1
phosphatase activity	1
negative regulation of dephosphorylation	1
negative regulation of hydrolase activity	1
cellular process	1
supramolecular fiber organization	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
negative regulation of protein kinase activity	1
regulation of protein autophosphorylation	1
protein autophosphorylation	1
sodium:proton antiporter activity	1
positive regulation of sodium ion transmembrane transporter activity	1
protein import into nucleus	1
regulation of protein import into nucleus	1
negative regulation of nucleocytoplasmic transport	1
negative regulation of intracellular protein transport	1
negative regulation of protein localization to nucleus	1

Protein interactions and networks

STRING

1809 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHP1	HS1BP3	Q53T59	763
CHP1	CER1	O95813	755
CHP1	SLC9A1	P19634	678
CHP1	KLF12	Q9Y4X4	668
CHP1	SLC9A3	P48764	628
CHP1	PLS3	P13797	593
CHP1	STK17B	O94768	567
CHP1	SLC9A2	Q9UBY0	563
CHP1	DENND1B	Q6P3S1	547
CHP1	CALML3	P27482	545
CHP1	SOS2	Q07890	541
CHP1	CALML6	Q8TD86	507
CHP1	CALML4	Q96GE6	507
CHP1	CALML5	Q9NZT1	507
CHP1	NCALD	P29554	500

IntAct

99 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
SLC9A3	CHP1	psi-mi:“MI:0407”(direct interaction)	0.650
CHP1	SLC9A1	psi-mi:“MI:0407”(direct interaction)	0.620
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
	CHP1	psi-mi:“MI:0407”(direct interaction)	0.560
GPAT4	CHP1	psi-mi:“MI:0915”(physical association)	0.560
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
	RBFOX2	psi-mi:“MI:0914”(association)	0.500
	CHP1	psi-mi:“MI:0915”(physical association)	0.500
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460
	SLC9A1	psi-mi:“MI:0407”(direct interaction)	0.440
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
HA	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): CHP1 (Affinity Capture-RNA), CHP1 (Affinity Capture-RNA), CHP1 (Affinity Capture-RNA), CHP1 (Proximity Label-MS), CHP1 (Affinity Capture-MS), CHP1 (Affinity Capture-MS), CHP1 (Affinity Capture-MS), CHP1 (Reconstituted Complex), CHP1 (Affinity Capture-Western), CHP1 (Affinity Capture-MS), CHP1 (Affinity Capture-MS), CHP1 (Affinity Capture-MS), CHP1 (Proximity Label-MS), CHP1 (Proximity Label-MS), CHP1 (Affinity Capture-MS)

ESM2 similar proteins: A0AVX7, A2VEI2, F4J0W4, O43745, O70200, O73761, O73762, P04354, P04467, P05937, P07171, P12658, P22728, P41044, P43080, P43081, P46065, P51177, P55008, P61022, P61023, P79880, P81076, Q0V9B1, Q1LWZ0, Q298L5, Q3KQ77, Q3SYS6, Q3T024, Q4R760, Q4V7T8, Q5R4V1, Q5R7F0, Q5TM25, Q5U554, Q5ZM44, Q6P8Y1, Q810D1, Q8IMX7, Q8R426

Diamond homologs: A0AVX7, O43745, P42322, P61022, P61023, Q0V9B1, Q3SYS6, Q54MF3, Q5R7F0, Q5U554, Q5ZM44, Q6FLU4, Q757B7, Q810D1, Q874T7, Q96BS2, Q99653, Q9D869, Q9JKL5, A0A509AFG4, A9JTH1, B3DLU1, B3VSB7, B5FZ84, C7A276, G5EDN6, O75838, O81223, O81445, P04464, P05419, P06707, P06708, P0CM54, P0CM55, P25296, P28470, P29104, P29105, P29291

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by SCF-KIT	5	18.5×	2e-04
R-HSA-425393	9	17.4×	4e-07
SLC-mediated transmembrane transport	11	9.7×	2e-06
Transport of small molecules	11	4.1×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
sodium ion import across plasma membrane	5	33.6×	1e-04
regulation of intracellular pH	5	32.4×	1e-04
amino acid transport	7	23.5×	1e-05
insulin receptor signaling pathway	6	14.3×	7e-04
sodium ion transmembrane transport	5	10.9×	8e-03
monoatomic ion transport	6	10.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
632545	NM_007236.5(CHP1):c.52AAG[1] (p.Lys19del)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1306 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:41243691:T:C	L31P	1.000
15:41243700:G:C	R34P	1.000
15:41243702:T:C	F35L	1.000
15:41243703:T:C	F35S	1.000
15:41243704:C:A	F35L	1.000
15:41243704:C:G	F35L	1.000
15:41243712:T:C	L38P	1.000
15:41243736:T:A	L46H	1.000
15:41256921:T:C	F51S	1.000
15:41256939:T:A	L57H	1.000
15:41256939:T:C	L57P	1.000
15:41256949:C:A	N60K	1.000
15:41256949:C:G	N60K	1.000
15:41256950:C:T	P61S	1.000
15:41256951:C:A	P61Q	1.000
15:41256954:T:A	L62Q	1.000
15:41256966:T:A	I66N	1.000
15:41256966:T:C	I66T	1.000
15:41256966:T:G	I66S	1.000
15:41262781:T:C	F83L	1.000
15:41262782:T:C	F83S	1.000
15:41262783:C:A	F83L	1.000
15:41262783:C:G	F83L	1.000
15:41262796:G:C	A88P	1.000
15:41262802:T:C	F90L	1.000
15:41262803:T:C	F90S	1.000
15:41262804:C:A	F90L	1.000
15:41262804:C:G	F90L	1.000
15:41262876:A:C	K114N	1.000
15:41262876:A:T	K114N	1.000

dbSNP variants (sampled 300 via entrez): RS1000027802 (15:41255420 C>G), RS1000085566 (15:41249909 G>T), RS1000184479 (15:41273085 T>C), RS1000204348 (15:41282084 C>T), RS1000219978 (15:41257983 C>G,T), RS1000224084 (15:41274073 G>A,C), RS1000322761 (15:41264664 C>T), RS1000407298 (15:41229619 T>C), RS1000437592 (15:41269347 A>G), RS1000441381 (15:41255658 A>T), RS1000453414 (15:41276730 G>A), RS1000637819 (15:41233109 C>A,T), RS1000693781 (15:41245943 T>C), RS1000704490 (15:41239582 G>C,T), RS1000741057 (15:41242126 T>A)

Disease associations

OMIM: gene MIM:606988 | disease phenotypes: MIM:618438

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic ataxia 9, autosomal recessive	Limited	Unknown

Mondo (1): spastic ataxia 9, autosomal recessive (MONDO:0032753)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067141 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
bisphenol B	increases expression	1
abrine	decreases expression	1
Decitabine	affects methylation	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Amphotericin B	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Thiram	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Isotretinoin	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651113	Binding	Binding affinity to human CHP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1LZ	Abcam K-562 CHP1 KO	Cancer cell line	Female
CVCL_D2IJ	Abcam Raji CHP1 KO	Cancer cell line	Male
CVCL_UQ31	Abcam Jurkat CHP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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