RBSN

Summary

RBSN (rabenosyn, RAB effector, HGNC:20759) is a protein-coding gene on chromosome 3p25.1, encoding Rabenosyn-5 (Q9H1K0). Rab4/Rab5 effector protein acting in early endocytic membrane fusion and membrane trafficking of recycling endosomes. It is a selective cancer dependency (DepMap: 26.7% of cell lines).

This gene encodes a protein that belongs to the FYVE zinc finger family of proteins. The encoded protein interacts with Ras-related proteins that regulate membrane trafficking. A missense mutation in this gene is associated with a defect in the early endocytic pathway. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 64145 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Kariminejad neurodevelopmental syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 149 total — 3 pathogenic
• Phenotypes (HPO): 110
• Cancer dependency (DepMap): dependent in 26.7% of screened cell lines
• MANE Select transcript: NM_022340

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20759
Approved symbol	RBSN
Name	rabenosyn, RAB effector
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131381
Ensembl biotype	protein_coding
OMIM	609511
Entrez	64145

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000253699, ENST00000426541, ENST00000441057, ENST00000449050, ENST00000449964, ENST00000463214, ENST00000476527, ENST00000483098, ENST00000507357, ENST00000905152, ENST00000938328, ENST00000938329, ENST00000938330, ENST00000938331, ENST00000938332, ENST00000945190, ENST00000945191, ENST00000945192, ENST00000945193, ENST00000945194

RefSeq mRNA: 2 — MANE Select: NM_022340 NM_001302378, NM_022340

CCDS: CCDS2623

Canonical transcript exons

ENST00000253699 — 14 exons

Exon	Start	End
ENSE00000901295	15075606	15075710
ENSE00000901296	15077062	15077164
ENSE00000901297	15078075	15078161
ENSE00001242854	15070073	15074930
ENSE00001399837	15096535	15096710
ENSE00001400873	15098119	15098274
ENSE00001426996	15099035	15099148
ENSE00001748893	15082367	15082608
ENSE00003465398	15095973	15096288
ENSE00003540713	15085000	15085045
ENSE00003564251	15080732	15080802
ENSE00003571118	15085861	15085961
ENSE00003648832	15090399	15090539
ENSE00003677467	15084735	15084896

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1791 / max 157.8898, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41242	12.1791	1797

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.62	gold quality
left ventricle myocardium	UBERON:0006566	97.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.85	gold quality
upper arm skin	UBERON:0004263	95.35	gold quality
tibialis anterior	UBERON:0001385	94.99	gold quality
cerebellar vermis	UBERON:0004720	94.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.30	gold quality
middle temporal gyrus	UBERON:0002771	94.29	gold quality
medial globus pallidus	UBERON:0002477	93.70	gold quality
corpus callosum	UBERON:0002336	93.69	gold quality
postcentral gyrus	UBERON:0002581	93.47	gold quality
globus pallidus	UBERON:0001875	93.27	gold quality
parietal lobe	UBERON:0001872	93.26	gold quality
entorhinal cortex	UBERON:0002728	93.06	gold quality
superior frontal gyrus	UBERON:0002661	92.60	gold quality
sural nerve	UBERON:0015488	92.41	gold quality
seminal vesicle	UBERON:0000998	92.28	gold quality
visceral pleura	UBERON:0002401	92.19	gold quality
parietal pleura	UBERON:0002400	91.91	gold quality
medulla oblongata	UBERON:0001896	91.80	gold quality
layer of synovial tissue	UBERON:0007616	91.73	gold quality
inferior vagus X ganglion	UBERON:0005363	91.71	gold quality
superior vestibular nucleus	UBERON:0007227	91.69	gold quality
kidney epithelium	UBERON:0004819	91.58	silver quality
substantia nigra pars reticulata	UBERON:0001966	91.48	gold quality
pons	UBERON:0000988	91.45	gold quality
lateral globus pallidus	UBERON:0002476	91.43	gold quality
cartilage tissue	UBERON:0002418	91.31	gold quality
subthalamic nucleus	UBERON:0001906	91.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting RBSN, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• results demonstrate that even the structurally similar effector domains in rabenosyn-5 can achieve highly selective recognition of distinct subsets of Rab GTPases exclusively through interactions with the switch and interswitch regions (PMID:16034420)
• Data implicate hVps45 and Rabenosyn-5 in post early endosome transport, and suggest that their interaction serves as a nexus to promote bidirectional transport along the endosome-to-recycling compartment and endosome-to-Golgi axes. (PMID:19931244)
• transferrin receptors are delivered selectively from clathrin-coated pits on the plasma membrane into a specific subpopulation of endosomes enriched in the multivalent Rab GTPase and phosphoinositide-binding protein Rabenosyn-5. (PMID:22308388)
• A functional defect in the endocytic pathway resulting from a point mutation in Rabenosyn-5 leads to severe multi-organ disorder. (PMID:25233840)
• 3 consanguineous siblings with syndromic congenital myelofibrosis had a variant (NM_022340.3:c.289G>C; NP_001289307.1:p.Gly97Arg) in RBSN. All 3 were homozygous; the parents and a cousin were heterozygous. RBSN loss of function causes a severe syndromic form of congenital myelofibrosis, confirming that rabenosyn-5 plays a vital role in human development and hematopoiesis. (PMID:29784638)
• The Rab-binding module of FERARI (factors for endosome recycling and Rab interactions) consists of Rab11FIP5 and rabenosyn-5, while the SNARE-interacting module comprises VPS45 and VIPAS39. (PMID:31988382)
• RABENOSYN separation-of-function mutations uncouple endosomal recycling from lysosomal degradation, causing a distinct Mendelian disorder. (PMID:35652444)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbsn	ENSDARG00000078215
mus_musculus	Rbsn	ENSMUSG00000014550
rattus_norvegicus	Rbsn	ENSRNOG00000011391
drosophila_melanogaster	Rbsn-5	FBGN0261064
caenorhabditis_elegans		WBGENE00021538

Protein

Protein identifiers

Rabenosyn-5 — Q9H1K0 (reviewed: Q9H1K0)

Alternative names: 110 kDa protein, FYVE finger-containing Rab5 effector protein rabenosyn-5, RAB effector RBSN, Zinc finger FYVE domain-containing protein 20

All UniProt accessions (5): C9JZZ1, D6RD50, Q9H1K0, F8WE50, H7C204

UniProt curated annotations — full annotation on UniProt →

Function. Rab4/Rab5 effector protein acting in early endocytic membrane fusion and membrane trafficking of recycling endosomes. Required for endosome fusion either homotypically or with clathrin coated vesicles. Plays a role in the lysosomal trafficking of CTSD/cathepsin D from the Golgi to lysosomes. Also promotes the recycling of transferrin directly from early endosomes to the plasma membrane. Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate (PtdInsP3). Plays a role in the recycling of transferrin receptor to the plasma membrane.

Subunit / interactions. Interacts with EHD1, RAB4A, RAB5A, RAB14, RAB22A, RAB24 and VPS45. Binds simultaneously to RAB4A and RAB5A in vitro. Interacts with RAB4A and RAB5A that has been activated by GTP binding.

Subcellular location. Cell membrane. Early endosome membrane.

Disease relevance. Kariminejad neurodevelopmental syndrome (KAREVS) [MIM:620937] An autosomal recessive disorder characterized by global developmental delay, progressive muscle weakness, facial dysmorphisms, ophthalmoplegia and intellectual disability. The disease is caused by variants affecting the gene represented in this entry. Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities (MFANDO) [MIM:620939] An autosomal recessive disorder characterized by neutropenia, anemia, thrombocytopenia, and myelofibrosis. Additional features include global developmental delay, osteopenia, delayed bone age, ocular abnormalities, and facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry. The genetic variation NM_022340.3:c.289G>C producing the missense variant p.Gly97Arg has been shown to predominantly affect splicing, leading to skipping of exon 5 or presence of an alternative exon 5a or retention of exon 5 and its neighboring introns. In one family, the homozygous proband showed no normally spliced transcript, while in her heterozygous father, normal transcripts represented 45%. The protein resulting from this aberrant splicing may be unstable, as it could not be detected in the proband’s cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H1K0-1	1	yes
Q9H1K0-2	2

RefSeq proteins (2): NP_001289307, NP_071735* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000306	Znf_FYVE	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR017455	Znf_FYVE-rel	Domain
IPR021565	Rbsn_Rab-bd	Domain
IPR036531	Rbsn_Rab-bd_sf	Homologous_superfamily
IPR052727	Rab4/Rab5_effector	Family

Pfam: PF01363, PF11464, PF16601

UniProt features (52 total): binding site 8, region of interest 7, modified residue 7, sequence variant 7, compositionally biased region 6, helix 4, coiled-coil region 2, zinc finger region 2, splice variant 2, mutagenesis site 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1Z0J	X-RAY DIFFRACTION	1.32
1YZM	X-RAY DIFFRACTION	1.5
1Z0K	X-RAY DIFFRACTION	1.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1K0-F1	69.02	0.27

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 (8): 163; 166; 179; 182; 187; 190; 252; 255

Post-translational modifications (7): 2, 3, 215, 219, 226, 230, 684

Mutagenesis-validated functional residues (2):

Position	Phenotype
626–628	reduces the interaction with ehd1. abolishes the interaction with ehd1; when associated with 662-apa-664.
662–664	reduces the interaction with ehd1. abolishes the interaction with ehd1; when associated with 626-apa-628.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 398 (showing top): GOBP_REGULATION_OF_GOLGI_ORGANIZATION, WANG_CLIM2_TARGETS_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_LYSOSOMAL_TRANSPORT, TATTATA_MIR374, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, ATGCAGT_MIR217, GOMF_GTPASE_BINDING, AAAGGGA_MIR204_MIR211, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_GOLGI_TO_VACUOLE_TRANSPORT, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_EARLY_ENDOSOME_TO_GOLGI_TRANSPORT, KEGG_ENDOCYTOSIS

GO Biological Process (5): protein transport (GO:0015031), endosomal transport (GO:0016197), early endosome to Golgi transport (GO:0034498), Golgi to lysosome transport (GO:0090160), regulation of Golgi organization (GO:1903358)

GO Molecular Function (5): zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), phosphatidylinositol-3-phosphate binding (GO:0032266), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): endosome (GO:0005768), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), early endosome membrane (GO:0031901), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Toll-like Receptor Cascades	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome	2
cellular anatomical structure	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
vesicle-mediated transport	1
intracellular transport	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
Golgi to vacuole transport	1
lysosomal transport	1
cytosolic transport	1
Golgi organization	1
regulation of organelle organization	1
transition metal ion binding	1
GTPase binding	1
phosphatidylinositol phosphate binding	1
binding	1
cation binding	1
endomembrane system	1
cytoplasmic vesicle	1
cytoplasm	1
membrane	1
cell periphery	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
early endosome	1
endosome membrane	1
extracellular vesicle	1

Protein interactions and networks

STRING

1344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBSN	VPS45	Q9NRW7	998
RBSN	RAB5A	P20339	993
RBSN	RAB4A	P20338	991
RBSN	EHD1	Q9H4M9	960
RBSN	RABEP1	Q15276	834
RBSN	RABGEF1	Q9UJ41	802
RBSN	RAB11FIP2	Q7L804	794
RBSN	EHD3	Q9NZN3	776
RBSN	STX6	O43752	736
RBSN	RAB22A	Q9UL26	719
RBSN	SNAP29	O95721	715
RBSN	EHBP1	Q8NDI1	714
RBSN	APPL1	Q9UKG1	705
RBSN	EHD4	Q9H223	694
RBSN	ANKFY1	Q9P2R3	676

IntAct

52 interactions, top by confidence:

A	B	Type	Score
RBSN	VPS45	psi-mi:“MI:0915”(physical association)	0.800
VPS45	RBSN	psi-mi:“MI:0915”(physical association)	0.800
EHD1	RBSN	psi-mi:“MI:0915”(physical association)	0.730
EHD1	RBSN	psi-mi:“MI:0403”(colocalization)	0.730
RBSN	EHD3	psi-mi:“MI:0915”(physical association)	0.660
RAB4A	RBSN	psi-mi:“MI:2364”(proximity)	0.660
RAB4A	RBSN	psi-mi:“MI:0915”(physical association)	0.660
RAB5C	RBSN	psi-mi:“MI:0915”(physical association)	0.610
RBSN	RAB5C	psi-mi:“MI:0407”(direct interaction)	0.610
RBSN	RAB22A	psi-mi:“MI:0915”(physical association)	0.400
RBSN	EHD2	psi-mi:“MI:0915”(physical association)	0.370
RBSN	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
Immt	GOSR1	psi-mi:“MI:0914”(association)	0.350
RAB5A	EEA1	psi-mi:“MI:0914”(association)	0.350
RBSN	LMX1B	psi-mi:“MI:0914”(association)	0.350
MUSK	DNAJC13	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
rep	CNOT1	psi-mi:“MI:0914”(association)	0.350
RBSN	ZNF747	psi-mi:“MI:0914”(association)	0.350
RBSN	MYH1	psi-mi:“MI:0914”(association)	0.350
E2F3	MYO1C	psi-mi:“MI:0914”(association)	0.350
NINL	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
RAB5A	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (109): RBSN (Two-hybrid), RBSN (Reconstituted Complex), RBSN (Two-hybrid), RBSN (Two-hybrid), RBSN (Co-fractionation), RBSN (Proximity Label-MS), RBSN (Affinity Capture-MS), VPS45 (Affinity Capture-MS), EHD3 (Affinity Capture-MS), EHD4 (Affinity Capture-MS), AVIL (Affinity Capture-MS), PCDHA4 (Affinity Capture-MS), IFFO1 (Affinity Capture-MS), EHD1 (Affinity Capture-MS), LMX1B (Affinity Capture-MS)

ESM2 similar proteins: A1L520, A5DDB7, A8WSQ9, O80925, O82171, O94601, P03197, P0C717, P35197, P38682, P53604, P93755, Q09237, Q09446, Q09531, Q0CGL5, Q0WQ57, Q10367, Q17R07, Q20374, Q24546, Q28CM8, Q3KST5, Q3MID3, Q4KLN7, Q4KMC9, Q4R4C9, Q5R787, Q5RAT7, Q62848, Q80Y56, Q8GWI5, Q8H100, Q8N6H7, Q8N6T3, Q95XU6, Q95Y36, Q99K28, Q9C950, Q9D8S3

Diamond homologs: A0JMD2, A8QCE4, B0G126, O13786, O59722, O95405, O96838, Q0P4S0, Q15075, Q54CH1, Q54LD5, Q54TC3, Q5R5R4, Q69ZL1, Q6VNB8, Q6ZPK7, Q6ZV73, Q7Z3T8, Q7Z6J4, Q80U44, Q80Y56, Q8BIJ7, Q8BL66, Q8BY35, Q8IZQ1, Q8R4C2, Q8WXA3, Q96T51, Q9H1K0, Q9HCC9, Q9LUM0, Q9Y2I7, Q9Z1T6, A0A0D1E015, A8XJZ8, B0WAQ0, B3MT31, B3P851, B4G2G5, B4IC49

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MAPK14	up-regulates	RBSN	phosphorylation
RBSN	“form complex”	“Early Endosome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
Clathrin-mediated endocytosis	5	11.8×	4e-03
Factors involved in megakaryocyte development and platelet production	5	9.2×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
endocytosis	9	19.0×	4e-07
cilium assembly	6	9.8×	7e-03
intracellular protein transport	6	8.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	110
Likely benign	8
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3340062	NM_022340.4(RBSN):c.289G>C (p.Gly97Arg)	Pathogenic
3340063	NM_022340.4(RBSN):c.547G>A (p.Gly183Arg)	Pathogenic
3340064	NM_022340.4(RBSN):c.538C>G (p.Arg180Gly)	Pathogenic

SpliceAI

2566 predictions. Top by Δscore:

Variant	Effect	Δscore
3:15074927:CAGC:C	acceptor_gain	1.0000
3:15074928:AGC:A	acceptor_gain	1.0000
3:15074931:C:CC	acceptor_gain	1.0000
3:15074932:T:G	acceptor_loss	1.0000
3:15075599:CACT:C	donor_loss	1.0000
3:15075602:T:TA	donor_loss	1.0000
3:15075603:CA:C	donor_loss	1.0000
3:15075604:A:AC	donor_gain	1.0000
3:15075604:AC:A	donor_loss	1.0000
3:15075605:C:CA	donor_gain	1.0000
3:15075605:CT:C	donor_gain	1.0000
3:15075605:CTTGT:C	donor_gain	1.0000
3:15075626:T:TA	donor_gain	1.0000
3:15075706:TTTTC:T	acceptor_gain	1.0000
3:15075707:TTTC:T	acceptor_gain	1.0000
3:15075709:TC:T	acceptor_gain	1.0000
3:15075710:CC:C	acceptor_gain	1.0000
3:15075711:C:CA	acceptor_loss	1.0000
3:15075711:C:CC	acceptor_gain	1.0000
3:15075712:T:C	acceptor_loss	1.0000
3:15077165:C:CC	acceptor_gain	1.0000
3:15077170:T:C	acceptor_gain	1.0000
3:15077170:T:TC	acceptor_gain	1.0000
3:15078069:CCTTA:C	donor_loss	1.0000
3:15078070:CTTAC:C	donor_loss	1.0000
3:15078071:TTAC:T	donor_loss	1.0000
3:15078072:TA:T	donor_loss	1.0000
3:15078073:ACCTT:A	donor_loss	1.0000
3:15078157:CAGCA:C	acceptor_gain	1.0000
3:15078158:AGCA:A	acceptor_gain	1.0000

AlphaMissense

5164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:15082444:A:G	C255R	1.000
3:15084774:A:G	C187R	1.000
3:15084785:C:A	G183V	1.000
3:15084785:C:T	G183E	1.000
3:15084786:C:A	G183W	1.000
3:15084787:G:C	C182W	1.000
3:15084788:C:T	C182Y	1.000
3:15084789:A:G	C182R	1.000
3:15084796:G:C	C179W	1.000
3:15084797:C:G	C179S	1.000
3:15084797:C:T	C179Y	1.000
3:15084798:A:G	C179R	1.000
3:15084798:A:T	C179S	1.000
3:15084799:G:C	H178Q	1.000
3:15084799:G:T	H178Q	1.000
3:15084801:G:C	H178D	1.000
3:15084823:G:C	F170L	1.000
3:15084823:G:T	F170L	1.000
3:15084824:A:G	F170S	1.000
3:15084825:A:G	F170L	1.000
3:15084844:A:C	C163W	1.000
3:15084845:C:G	C163S	1.000
3:15084846:A:G	C163R	1.000
3:15084846:A:T	C163S	1.000
3:15084854:A:T	V160D	1.000
3:15084871:C:A	W154C	1.000
3:15084871:C:G	W154C	1.000
3:15084873:A:G	W154R	1.000
3:15084873:A:T	W154R	1.000
3:15085044:A:G	L131P	1.000

dbSNP variants (sampled 300 via entrez): RS1000077294 (3:15098049 TG>T), RS1000196032 (3:15080037 G>T), RS1000205124 (3:15092392 GTTTT>G,GTTT,GTTTTT), RS1000206691 (3:15083445 C>A,T), RS1000236334 (3:15083827 C>A,T), RS1000326192 (3:15077618 G>T), RS1000436066 (3:15076098 C>T), RS1000553332 (3:15097804 G>A), RS1000573030 (3:15086573 T>C), RS1000592102 (3:15085100 C>T), RS1000696928 (3:15090779 T>C), RS1000867085 (3:15076339 G>A), RS1000940811 (3:15071127 C>A), RS1000971720 (3:15071402 C>A), RS1001039710 (3:15093359 G>A,C)

Disease associations

OMIM: gene MIM:609511 | disease phenotypes: MIM:620937, MIM:620939

GenCC curated gene-disease

Disease	Classification	Inheritance
Kariminejad neurodevelopmental syndrome	Strong	Autosomal recessive
congenital neutropenia-myelofibrosis-nephromegaly syndrome	Supportive	Autosomal recessive

Mondo (3): Kariminejad neurodevelopmental syndrome (MONDO:0975795), myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities (MONDO:0975797), congenital neutropenia-myelofibrosis-nephromegaly syndrome (MONDO:0014118)

Orphanet (0):

HPO phenotypes

110 total (30 of 110 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000064	Hypoplastic labia minora
HP:0000105	Enlarged kidney
HP:0000160	Narrow mouth
HP:0000179	Thick lower lip vermilion
HP:0000189	Narrow palate
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000286	Epicanthus
HP:0000308	Microretrognathia
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000437	Depressed nasal tip
HP:0000448	Prominent nose
HP:0000482	Microcornea
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000526	Aniridia
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000592	Blue sclerae

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001471_3	Alcohol and nicotine co-dependence	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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