NBAS

Summary

NBAS (NBAS subunit of NRZ tethering complex, HGNC:15625) is a protein-coding gene on chromosome 2p24.3, encoding NBAS subunit of NRZ tethering complex (A2RRP1). Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER. It is a selective cancer dependency (DepMap: 55.6% of cell lines).

This gene encodes a protein with two leucine zipper domains, a ribosomal protein S14 signature domain and a Sec39 like domain. The protein is thought to be involved in Golgi-to-ER transport. Mutations in this gene are associated with short stature, optic nerve atrophy, and Pelger-Huet anomaly.

Source: NCBI Gene 51594 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short stature-optic atrophy-Pelger-Huët anomaly syndrome (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 2,885 total — 152 pathogenic, 97 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 55.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_015909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15625
Approved symbol	NBAS
Name	NBAS subunit of NRZ tethering complex
Location	2p24.3
Locus type	gene with protein product
Status	Approved
Aliases	NAG
Ensembl gene	ENSG00000151779
Ensembl biotype	protein_coding
OMIM	608025
Entrez	51594

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 13 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000281513, ENST00000423602, ENST00000427792, ENST00000429842, ENST00000433283, ENST00000442506, ENST00000485694, ENST00000700061, ENST00000700062, ENST00000700063, ENST00000700064, ENST00000700065, ENST00000700066, ENST00000700067, ENST00000700068, ENST00000700069, ENST00000700070, ENST00000700071, ENST00000700072, ENST00000700073, ENST00000901626, ENST00000914564, ENST00000914565, ENST00000957312

RefSeq mRNA: 1 — MANE Select: NM_015909 NM_015909

CCDS: CCDS1685

Canonical transcript exons

ENST00000281513 — 52 exons

Exon	Start	End
ENSE00000913894	15218773	15218968
ENSE00000913895	15232422	15232511
ENSE00001070338	15467664	15467804
ENSE00001070339	15474067	15474324
ENSE00001070341	15468382	15468533
ENSE00001070344	15478226	15478289
ENSE00001070345	15475687	15475880
ENSE00001070751	15539223	15539356
ENSE00001070755	15504145	15504213
ENSE00001070759	15511212	15511350
ENSE00001070761	15488894	15489022
ENSE00001070764	15536418	15536551
ENSE00001148350	15275484	15275818
ENSE00001148359	15276851	15277101
ENSE00001148368	15287073	15287183
ENSE00001148376	15292537	15292766
ENSE00001148387	15308216	15308353
ENSE00001148396	15309171	15309247
ENSE00001148403	15327750	15327870
ENSE00001148409	15328199	15328312
ENSE00001148419	15330598	15330765
ENSE00001148428	15351992	15352081
ENSE00001148436	15353553	15353710
ENSE00001148455	15366580	15366693
ENSE00001148465	15379602	15379831
ENSE00001148471	15383215	15383317
ENSE00001155454	15238468	15238686
ENSE00001185164	15356303	15356416
ENSE00001241386	15424315	15424468
ENSE00001241473	15234545	15234747
ENSE00001241591	15394227	15394349
ENSE00001241610	15415546	15415719
ENSE00001241616	15417527	15417712
ENSE00001241632	15427711	15427794
ENSE00001241640	15461201	15461337
ENSE00001241646	15461687	15461791
ENSE00001241653	15467329	15467407
ENSE00001241669	15473222	15473347
ENSE00001241708	15534543	15534641
ENSE00001241726	15551493	15551536
ENSE00001241736	15553426	15553473
ENSE00001241744	15554061	15554138
ENSE00001241752	15556783	15556819
ENSE00001241760	15558580	15558634
ENSE00001241831	15561188	15561334
ENSE00001309962	15402168	15402301
ENSE00001320513	15396413	15396475
ENSE00001800603	15166916	15167323
ENSE00003580606	15178988	15179116
ENSE00003625125	15190264	15190403
ENSE00003638141	15186742	15186880
ENSE00003789024	15374608	15374720

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 95.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.0393 / max 958.2017, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26979	31.0217	1817
26969	0.0176	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.70	gold quality
ventricular zone	UBERON:0003053	93.33	gold quality
gluteal muscle	UBERON:0002000	92.83	gold quality
tendon	UBERON:0000043	92.74	gold quality
apex of heart	UBERON:0002098	92.37	gold quality
triceps brachii	UBERON:0001509	92.24	gold quality
left testis	UBERON:0004533	92.04	gold quality
right testis	UBERON:0004534	92.04	gold quality
stromal cell of endometrium	CL:0002255	91.86	gold quality
sperm	CL:0000019	91.84	gold quality
corpus callosum	UBERON:0002336	91.67	gold quality
parotid gland	UBERON:0001831	91.45	gold quality
male germ cell	CL:0000015	91.33	gold quality
testis	UBERON:0000473	91.15	gold quality
adrenal tissue	UBERON:0018303	91.11	gold quality
adenohypophysis	UBERON:0002196	90.91	gold quality
ganglionic eminence	UBERON:0004023	90.81	gold quality
pituitary gland	UBERON:0000007	90.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.53	gold quality
nucleus accumbens	UBERON:0001882	90.52	gold quality
middle temporal gyrus	UBERON:0002771	90.29	gold quality
heart left ventricle	UBERON:0002084	90.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.07	gold quality
cardiac ventricle	UBERON:0002082	90.05	gold quality
cortical plate	UBERON:0005343	89.98	gold quality
right frontal lobe	UBERON:0002810	89.97	gold quality
putamen	UBERON:0001874	89.87	gold quality
caudate nucleus	UBERON:0001873	89.83	gold quality
body of pancreas	UBERON:0001150	89.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

10 targeting NBAS, 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-450B-5P	99.92	71.48	3175
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-3918	96.13	64.65	1300

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 55.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• There may be a subset of NB in which enhanced DDX1 and low-NAG expression consequent to DDX1 co-amplification without NAG amplification contributes to susceptibility to intensive therapy. (PMID:17028906)
• Results together suggest that NAG links between p31 and ZW10-RINT-1 and is involved in Golgi-to-ER transport. (PMID:19369418)
• Defects in NAG-ELMO1 is associated with leukemic progression. (PMID:19407829)
• These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huet anomaly. (PMID:20577004)
• DHX34 and NBAS act in concert with core nonsense-mediated mRNA decay factors to co-regulate a large number of endogenous RNA targets. (PMID:23828042)
• Data indicate that expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4 in neuroblastoma. (PMID:23991058)
• Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy. (PMID:26073778)
• NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina. (PMID:26286438)
• variants in NBAS, are reported as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS. (PMID:27789416)
• A novel compound heterozygous mutations of NBAS (NM_015909.3): c.680A > C (p.His227Pro) were identified in two siblings with acute liver failure. (PMID:28576691)
• NBAS was the only candidate gene mutated in more than one patient. All NBAS mutations were novel and predictedly pathogenic. Of these mutations, 3 lay in distal (C-terminal) regions of NBAS, a novel distribution. Unlike the 2 patients without NBAS mutations, the 3 patients with confirmed NBAS mutations all suffered from a febrile illness before each episode of liver crisis (fever-related recurrent acute liver failure) (PMID:28629372)
• The age of the mutation in Yakutia was estimated to be about 804 +/- 140 years. The frequency of heterozygous carriers of mutation G5741–>A (R1914H) in gene NBAS was found, which averaged 13 per 1000 healthy Yakuts (PMID:29369590)
• A novel homozygous truncating mutation in the NBAS gene was identified in a family with Acrofrontofacionasal Dysostosis type 1. (PMID:29929043)
• Data report two unrelated subjects with a trait associated with defective NBAS function sharing a previously unreported pathogenic “synonymous” change demonstrated to affect proper NBAS transcript processing. Assessing the clinical features and signs of affected subjects with biallelic NBAS variants documents the occurrence of a recognizable facial profile for these patients. (PMID:30825388)
• Mutations in NBAS and SCYL1, genetic causes of recurrent liver failure in children: Three case reports and a literature review. (PMID:32146038)
• Severe SOPH syndrome due to a novel NBAS mutation in a 27-year-old woman-Review of this pleiotropic, autosomal recessive disorder: Mystery solved after two decades. (PMID:32297715)
• Novel compound heterozygous variants in the NBAS gene in a child with osteogenesis imperfecta and recurrent acute liver failure. (PMID:33542026)
• Characterization of a complex phenotype (fever-dependent recurrent acute liver failure and osteogenesis imperfecta) due to NBAS and P4HB variants. (PMID:33707149)
• NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency. (PMID:34386911)
• NBAS, a gene involved in cytotoxic degranulation, is recurrently mutated in pediatric hemophagocytic lymphohistiocytosis. (PMID:35902954)
• Modulation of NBAS-Related Functions in the Early Response to SARS-CoV-2 Infection. (PMID:36768954)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nbas	ENSDARG00000008593
mus_musculus	Nbas	ENSMUSG00000020576
rattus_norvegicus	Nbas	ENSRNOG00000024503
caenorhabditis_elegans	smgl-1	WBGENE00008990

Protein

Protein identifiers

NBAS subunit of NRZ tethering complex — A2RRP1 (reviewed: A2RRP1)

Alternative names: Neuroblastoma-amplified gene protein, Neuroblastoma-amplified sequence

All UniProt accessions (13): A2RRP1, A0A8V8TP87, A0A8V8TPL8, A0A8V8TPS6, A0A8V8TPT1, A0A8V8TQK6, A0A8V8TQX6, A0A8V8TQY0, H0Y5G7, H7BZR3, H7BZU5, H7C1U4, H7C1Y9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER. Required for normal embryonic development. May play a role in the nonsense-mediated decay pathway of mRNAs containing premature stop codons.

Subunit / interactions. Component of the NRZ complex composed of NBAS, ZW10 and RINT1/TIP20L; NRZ associates with SNAREs STX18, USE1, BNIP1/SEC20L and SEC22B (the assembly has been described as syntaxin 18 complex); links NRZ to SNARE USE1.

Subcellular location. Cytoplasm. Endoplasmic reticulum. Endoplasmic reticulum membrane.

Tissue specificity. Broadly expressed, with highest levels in heart and skeletal muscle, and lowest levels in liver, small intestine and thymus. Well expressed in retinal ganglion cells, epidermal skin cells, and leukocytes. Up-regulated together with N-myc in some neuroblastoma cell lines.

Disease relevance. Short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH) [MIM:614800] An autosomal recessive syndrome characterized by severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, abnormal nuclear shape in neutrophil granulocytes (Pelger-Huet anomaly), and optic atrophy with loss of visual acuity and color vision. The disease is caused by variants affecting the gene represented in this entry. Infantile liver failure syndrome 2 (ILFS2) [MIM:616483] A form of infantile liver failure syndrome, a life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis. The disease is caused by variants affecting the gene represented in this entry. NBAS mutations have been found in a multisystem disease affecting the liver, eye, immune system, connective tissue, and bone. Clinical manifestations include a progeroid appearance, short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, cervical instability, myelopathy, elevated transaminases, hypogammaglobulinemia, reduced natural killer cells, Pelger-Huet anomaly of granulocytes, and in some cases retinal dystrophy and optic atrophy.

Isoforms (2)

UniProt ID	Names	Canonical?
A2RRP1-1	1	yes
A2RRP1-2	2

RefSeq proteins (1): NP_056993* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011044	Quino_amine_DH_bsu	Homologous_superfamily
IPR013244	Sec39_domain	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR029145	NBAS_N	Domain
IPR054751	NBAS_C	Domain

Pfam: PF08314, PF15492, PF22913

UniProt features (52 total): sequence variant 29, sequence conflict 14, modified residue 3, repeat 2, region of interest 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2RRP1-F1	74.42	0.04

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 (3): 473, 475, 1057

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport

MSigDB gene sets: 234 (showing top): WANG_CLIM2_TARGETS_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, LASTOWSKA_COAMPLIFIED_WITH_MYCN, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, MORI_PLASMA_CELL_UP, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_NONSENSE_MEDIATED_DECAY, ACEVEDO_LIVER_CANCER_UP, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, PARENT_MTOR_SIGNALING_UP, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK

GO Biological Process (4): nuclear-transcribed mRNA catabolic process (GO:0000956), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), protein transport (GO:0015031), negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000623)

GO Molecular Function (2): SNARE binding (GO:0000149), protein binding (GO:0005515)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), Dsl1/NZR complex (GO:0070939), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Golgi-to-ER retrograde transport	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
mRNA catabolic process	1
Golgi vesicle transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
negative regulation of mRNA catabolic process	1
regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
protein binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vesicle tethering complex	1
endoplasmic reticulum protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NBAS	STX18	Q9P2W9	829
NBAS	USE1	Q9NZ43	594
NBAS	RINT1	Q6NUQ1	593
NBAS	RPS14	P06366	587
NBAS	ZW10	O43264	560
NBAS	SMG5	Q9UPR3	530
NBAS	SMG9	Q9H0W8	525
NBAS	SMG6	Q86US8	517
NBAS	DHX34	Q14147	509
NBAS	UPF2	Q9HAU5	503
NBAS	ICE1	Q9Y2F5	498
NBAS	SMG8	Q8ND04	490
NBAS	SCAPER	Q9BY12	471
NBAS	MYCN	P04198	463
NBAS	UPF3A	Q9H1J1	437

IntAct

133 interactions, top by confidence:

A	B	Type	Score
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.830
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NBAS	ZW10	psi-mi:“MI:0914”(association)	0.720
ZW10	NBAS	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710

BioGRID (173): NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Two-hybrid), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS), NBAS (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KIZ8, A0A1L8GXY4, A0A571BF63, A0A8M9QN10, A2CEI4, A2RRP1, A4D1P6, A6H8T2, A9X1C6, B0FXQ5, B1WC10, B2KIQ4, B2RY71, B2RYI0, B7FF09, B7FF12, E9PYY5, F1QHZ6, Q1LXZ7, Q2HJE1, Q3UMY5, Q402B2, Q4V8G4, Q5R6T6, Q5RE88, Q5U1Z0, Q5VTH9, Q5XIZ9, Q5ZLL7, Q6DFC6, Q6DTM3, Q6GPB9, Q6P2C0, Q6TEN6, Q7TMQ7, Q7ZVR1, Q8BMG7, Q8BX17, Q8C147, Q8IWG1

Diamond homologs: A2RRP1, Q5TYW4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NBAS	“form complex”	“NRZ complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
COPI-dependent Golgi-to-ER retrograde traffic	11	21.0×	7e-10
COPII-mediated vesicle transport	5	14.1×	1e-03
R-HSA-425393	6	13.4×	4e-04
COPI-mediated anterograde transport	7	13.2×	9e-05
ER to Golgi Anterograde Transport	5	11.4×	2e-03
Golgi-to-ER retrograde transport	5	11.4×	2e-03
Intra-Golgi and retrograde Golgi-to-ER traffic	6	10.8×	8e-04
Transport to the Golgi and subsequent modification	5	8.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	11	51.5×	6e-14
intra-Golgi vesicle-mediated transport	7	51.2×	1e-08
endoplasmic reticulum to Golgi vesicle-mediated transport	10	18.9×	2e-08
monoatomic ion transport	5	10.8×	5e-03
intracellular protein transport	12	10.8×	1e-07
protein transport	8	4.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2885 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	152
Likely pathogenic	97
Uncertain significance	1011
Likely benign	1200
Benign	178

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013178	NM_015909.4(NBAS):c.6147-1G>T	Pathogenic
1013179	NM_015909.4(NBAS):c.4843C>T (p.Arg1615Ter)	Pathogenic
1032709	NM_015909.4(NBAS):c.5262del (p.Phe1754fs)	Pathogenic
1076261	NM_015909.4(NBAS):c.2827G>T (p.Glu943Ter)	Pathogenic
1172780	NM_015909.4(NBAS):c.4288C>T (p.Gln1430Ter)	Pathogenic
1323328	NM_015909.4(NBAS):c.1858A>T (p.Lys620Ter)	Pathogenic
1324782	NM_015909.4(NBAS):c.1141dup (p.Ile381fs)	Pathogenic
1335898	NM_015909.4(NBAS):c.1213C>T (p.Arg405Ter)	Pathogenic
1370335	NM_015909.4(NBAS):c.3913C>T (p.Gln1305Ter)	Pathogenic
1370419	NM_015909.4(NBAS):c.6751_6754del (p.Leu2251fs)	Pathogenic
1380706	NM_015909.4(NBAS):c.1268_1284del (p.Gly423fs)	Pathogenic
1382399	NM_015909.4(NBAS):c.2719C>T (p.Gln907Ter)	Pathogenic
1389306	NM_015909.4(NBAS):c.3728_3729dup (p.Leu1244fs)	Pathogenic
1391781	NM_015909.4(NBAS):c.5558del (p.Lys1853fs)	Pathogenic
1403703	NM_015909.4(NBAS):c.4370_4371delinsGA (p.Tyr1457Ter)	Pathogenic
1406108	NM_015909.4(NBAS):c.1628_1629insA (p.Ser544fs)	Pathogenic
1446416	NM_015909.4(NBAS):c.4437dup (p.Ile1480fs)	Pathogenic
1451402	NC_000002.11:g.(?15514712)(15564612_?)del	Pathogenic
1452313	NM_015909.4(NBAS):c.1267G>T (p.Gly423Ter)	Pathogenic
1452384	NM_015909.4(NBAS):c.2802G>A (p.Trp934Ter)	Pathogenic
1452860	NM_015909.4(NBAS):c.3751C>T (p.Gln1251Ter)	Pathogenic
1453321	NM_015909.4(NBAS):c.1283G>A (p.Trp428Ter)	Pathogenic
1453984	NC_000002.11:g.(?15427177)(15557856_?)del	Pathogenic
1456419	NM_015909.4(NBAS):c.5170_5171insTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCGAGACCATCCTGGCTAACAAGGTGAAANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAGAAAATAGAGCCC (p.Gln1724delinsLeuThrProValIleProAlaLeuTrpGluAlaGluAlaGlyGlySerTer)	Pathogenic
1456537	NM_015909.4(NBAS):c.4220_4230del (p.Leu1407fs)	Pathogenic
1456578	NM_015909.4(NBAS):c.2742dup (p.Leu915fs)	Pathogenic
1456868	NM_015909.4(NBAS):c.5734G>T (p.Glu1912Ter)	Pathogenic
1457243	NM_015909.4(NBAS):c.721dup (p.Thr241fs)	Pathogenic
1458355	NM_015909.4(NBAS):c.3562del (p.Leu1188fs)	Pathogenic
1458493	NM_015909.4(NBAS):c.6840G>C (p.Thr2280=)	Pathogenic

SpliceAI

11348 predictions. Top by Δscore:

Variant	Effect	Δscore
2:15190256:ATACT:A	donor_loss	1.0000
2:15190257:TACTT:T	donor_loss	1.0000
2:15190258:AC:A	donor_loss	1.0000
2:15190260:T:TC	donor_loss	1.0000
2:15190261:T:TG	donor_loss	1.0000
2:15190262:A:AC	donor_gain	1.0000
2:15190263:C:CA	donor_gain	1.0000
2:15190263:CA:C	donor_gain	1.0000
2:15190263:CACA:C	donor_gain	1.0000
2:15190263:CACAT:C	donor_gain	1.0000
2:15190400:CTAC:C	acceptor_gain	1.0000
2:15190401:TAC:T	acceptor_gain	1.0000
2:15190402:AC:A	acceptor_gain	1.0000
2:15190403:CC:C	acceptor_gain	1.0000
2:15190404:C:CC	acceptor_gain	1.0000
2:15232406:A:AC	donor_gain	1.0000
2:15232407:C:CC	donor_gain	1.0000
2:15232407:CTGTT:C	donor_gain	1.0000
2:15232417:CTTA:C	donor_loss	1.0000
2:15232418:TTA:T	donor_loss	1.0000
2:15232420:AC:A	donor_gain	1.0000
2:15232420:ACC:A	donor_gain	1.0000
2:15232421:CC:C	donor_gain	1.0000
2:15232421:CCC:C	donor_gain	1.0000
2:15232507:CACCA:C	acceptor_gain	1.0000
2:15232508:ACCA:A	acceptor_gain	1.0000
2:15232509:CCA:C	acceptor_gain	1.0000
2:15232509:CCAC:C	acceptor_gain	1.0000
2:15232510:CA:C	acceptor_gain	1.0000
2:15232510:CACTG:C	acceptor_gain	1.0000

AlphaMissense

15528 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:15473264:C:A	W561C	0.999
2:15473264:C:G	W561C	0.999
2:15473266:A:G	W561R	0.999
2:15473266:A:T	W561R	0.999
2:15474080:A:G	L529P	0.999
2:15473310:G:T	A546D	0.998
2:15475793:A:T	V412D	0.998
2:15539318:A:G	W140R	0.998
2:15539318:A:T	W140R	0.998
2:15473265:C:G	W561S	0.997
2:15473280:A:T	V556E	0.997
2:15536463:A:G	L201P	0.997
2:15292585:A:G	F1660S	0.996
2:15379815:A:G	L1126P	0.996
2:15473223:A:G	L575S	0.996
2:15473322:G:T	A542D	0.996
2:15475845:A:G	W395R	0.996
2:15475845:A:T	W395R	0.996
2:15536436:A:G	L210P	0.996
2:15553456:G:T	A102D	0.996
2:15292563:T:A	K1667N	0.995
2:15292563:T:G	K1667N	0.995
2:15308276:G:C	S1579R	0.995
2:15308276:G:T	S1579R	0.995
2:15308278:T:G	S1579R	0.995
2:15379658:G:C	S1178R	0.995
2:15379658:G:T	S1178R	0.995
2:15379660:T:G	S1178R	0.995
2:15468454:A:G	L602P	0.995
2:15468512:A:G	W583R	0.995

dbSNP variants (sampled 300 via entrez): RS1000000066 (2:14786576 T>C), RS1000001057 (2:15120785 T>C), RS1000005806 (2:14841745 G>A), RS1000010325 (2:15216189 A>G), RS1000014514 (2:15435201 T>C), RS1000020707 (2:15331101 T>G), RS1000021439 (2:15175060 G>A), RS1000022811 (2:15223097 G>A), RS1000028619 (2:14932664 A>T), RS1000034023 (2:15307896 G>C), RS1000036668 (2:15449634 G>T), RS1000038031 (2:15055909 C>G), RS1000045728 (2:15062602 G>A), RS1000046158 (2:15038073 A>G), RS1000047010 (2:15020556 C>T)

Disease associations

OMIM: gene MIM:608025 | disease phenotypes: MIM:616483, MIM:614800, MIM:613070, MIM:181500, MIM:615438, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
short stature-optic atrophy-Pelger-Huët anomaly syndrome	Definitive	Autosomal recessive
infantile liver failure syndrome 2	Strong	Autosomal recessive
hereditary hemophagocytic lymphohistiocytosis	Strong	Autosomal recessive

Mondo (13): infantile liver failure syndrome 2 (MONDO:0014659), short stature-optic atrophy-Pelger-Huët anomaly syndrome (MONDO:0013889), inherited retinal dystrophy (MONDO:0019118), acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (MONDO:0013111), optic atrophy (MONDO:0003608), neurodevelopmental disorder (MONDO:0700092), schizophrenia (MONDO:0005090), retinal disorder (MONDO:0005283), optic nerve disorder (MONDO:0002135), infantile liver failure (MONDO:0000023), Leber congenital amaurosis (MONDO:0018998), pituitary stalk interruption syndrome (MONDO:0019828), hereditary hemophagocytic lymphohistiocytosis (MONDO:0015541)

Orphanet (7): Short stature-optic atrophy-Pelger-Huët anomaly syndrome (Orphanet:391677), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (Orphanet:217371), Fever-associated acute infantile liver failure syndrome (Orphanet:464724), Leber congenital amaurosis (Orphanet:65), Pituitary stalk interruption syndrome (Orphanet:95496), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000520	Proptosis
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000648	Optic atrophy
HP:0000952	Jaundice
HP:0000954	Single transverse palmar crease
HP:0000973	Cutis laxa
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001620	Abnormally high-pitched voice
HP:0001638	Cardiomyopathy
HP:0001852	Sandal gap
HP:0001943	Hypoglycemia
HP:0001987	Hyperammonemia
HP:0002013	Vomiting

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001204_1	Response to platinum-based chemotherapy (carboplatin)	5.000000e-07
GCST002880_1	Recalcitrant atopic dermatitis	8.000000e-08
GCST002989_10	LDL peak particle diameter (total fat intake interaction)	4.000000e-06
GCST002989_16	LDL peak particle diameter (total fat intake interaction)	9.000000e-06
GCST006088_7	Familial squamous cell lung carcinoma	2.000000e-06
GCST007448_5	Normal facial asymmetry (angle of surface orientation score)	2.000000e-10
GCST008762_1	Intake of sweets	9.000000e-06
GCST008889_2	Systemising	3.000000e-07
GCST012298_13	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	7.000000e-06
GCST012299_6	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4.000000e-06
GCST012301_9	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	7.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:1000651	recalcitrant atopic dermatitis
EFO:0007677	LDL peak particle diameter measurement
EFO:0007678	total fat intake measurement
EFO:0006953	family history of lung cancer
EFO:0009751	facial asymmetry measurement
EFO:0010158	sugar consumption measurement
EFO:0010221	systemising measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D065886	Neurodevelopmental Disorders	F03.625
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D009901	Optic Nerve Diseases	C10.292.700; C11.640
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066529 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1019358	NBAS		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.39	Kd	40.65	nM	CHEMBL3752910
7.38	ED50	41.67	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148827: Binding affinity to human NBAS incubated for 45 mins by Kinobead based pull down assay	kd	0.0406	uM

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	4
Aflatoxin B1	decreases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
geldanamycin	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
bisphenol B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Potassium Dichromate	decreases expression	1
Thimerosal	decreases expression	1
Vitamin E	increases expression	1
Carboplatin	affects response to substance	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
CHEMBL5651869	Binding	Binding affinity to human NBAS 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

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_VS00	DHMCi004-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05744063	PHASE4	COMPLETED	A Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of pHLH in Treatment Experienced Chinese Patients
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT03312751	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00368355	PHASE2	COMPLETED	T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT01494103	PHASE1	ACTIVE_NOT_RECRUITING	Administration of Donor T Cells With the Caspase-9 Suicide Gene
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03827343	Not specified	ACTIVE_NOT_RECRUITING	Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer
NCT06587191	Not specified	ACTIVE_NOT_RECRUITING	Emapalumab Efficacy in Children With Primary Hemophagocytic Lymphohistiocytosis
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer