NDUFAB1

Summary

NDUFAB1 (NADH:ubiquinone oxidoreductase subunit AB1, HGNC:7694) is a protein-coding gene on chromosome 16p12.2, encoding Acyl carrier protein, mitochondrial (O14561). Carrier of the growing fatty acid chain in fatty acid biosynthesis. It is a selective cancer dependency (DepMap: 75.4% of cell lines).

Enables mitochondrial large ribosomal subunit binding activity. Involved in [2Fe-2S] cluster assembly and protein lipoylation. Located in mitochondrial inner membrane and nucleoplasm. Part of mitochondrial [2Fe-2S] assembly complex and respiratory chain complex I.

Source: NCBI Gene 4706 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 124 total — 26 pathogenic, 2 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 75.4% of screened cell lines
• MANE Select transcript: NM_005003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7694
Approved symbol	NDUFAB1
Name	NADH:ubiquinone oxidoreductase subunit AB1
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Aliases	SDAP, FASN2A, ACP, ACP1
Ensembl gene	ENSG00000004779
Ensembl biotype	protein_coding
OMIM	603836
Entrez	4706

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000007516, ENST00000484769, ENST00000562133, ENST00000567761, ENST00000570319, ENST00000882847, ENST00000882848

RefSeq mRNA: 1 — MANE Select: NM_005003 NM_005003

CCDS: CCDS10614

Canonical transcript exons

ENST00000007516 — 5 exons

Exon	Start	End
ENSE00001921040	23596123	23596316
ENSE00002593859	23581014	23581173
ENSE00003542392	23587197	23587319
ENSE00003579953	23585336	23585423
ENSE00003654432	23582276	23582375

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.3615 / max 1138.0454, expressed in 1826 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156779	104.3615	1826

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.77	gold quality
left ventricle myocardium	UBERON:0006566	99.53	gold quality
myocardium	UBERON:0002349	99.47	gold quality
apex of heart	UBERON:0002098	99.46	gold quality
cardiac ventricle	UBERON:0002082	99.42	gold quality
heart left ventricle	UBERON:0002084	99.41	gold quality
biceps brachii	UBERON:0001507	99.40	gold quality
cardiac atrium	UBERON:0002081	99.38	gold quality
right atrium auricular region	UBERON:0006631	99.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.31	gold quality
body of tongue	UBERON:0011876	99.31	gold quality
triceps brachii	UBERON:0001509	99.29	gold quality
vastus lateralis	UBERON:0001379	99.27	gold quality
quadriceps femoris	UBERON:0001377	99.24	gold quality
diaphragm	UBERON:0001103	99.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.21	gold quality
deltoid	UBERON:0001476	99.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.20	gold quality
heart	UBERON:0000948	99.17	gold quality
pons	UBERON:0000988	99.17	gold quality
vena cava	UBERON:0004087	99.15	gold quality
gluteal muscle	UBERON:0002000	99.07	gold quality
adult organism	UBERON:0007023	99.07	gold quality
mucosa of transverse colon	UBERON:0004991	99.05	gold quality
tibialis anterior	UBERON:0001385	98.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.89	gold quality
gastrocnemius	UBERON:0001388	98.88	gold quality
muscle organ	UBERON:0001630	98.88	gold quality
skeletal muscle organ	UBERON:0014892	98.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.87	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	3217.14
E-CURD-88	no	3.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

8 targeting NDUFAB1, 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-4789-3P	99.99	70.75	2484
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-6890-3P	97.50	65.71	997

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 75.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• The p49/STRAP and NDUFAB1 proteins interacted and co-localized with each other in the cell. (PMID:18230186)
• ACP has a dual role in mammalian mitochondrial function (PMID:19221180)
• The molecular structure of the human mitochondrial cysteine desulfurase complex consisting of two copies each of NFS1, ISD11, and acyl carrier protein has been described. (PMID:29983374)
• In this work, the structure of the human mitochondrial ACP-ISD11 heterodimer was determined at 2.0 A resolution. (PMID:31664822)
• Substrate Sequestration and Chain Flipping in Human Mitochondrial Acyl Carrier Protein. (PMID:38039071)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndufab1b	ENSDARG00000014915
danio_rerio	ndufab1a	ENSDARG00000058463
mus_musculus	Ndufab1	ENSMUSG00000030869
rattus_norvegicus	Ndufab1	ENSRNOG00000018129
drosophila_melanogaster	ND-ACP	FBGN0011361
caenorhabditis_elegans		WBGENE00013237

Paralogs (1): ZNF593 (ENSG00000142684)

Protein

Protein identifiers

Acyl carrier protein, mitochondrial — O14561 (reviewed: O14561)

Alternative names: CI-SDAP, NADH-ubiquinone oxidoreductase 9.6 kDa subunit

All UniProt accessions (4): O14561, H3BNE8, H3BNK3, I3L505

UniProt curated annotations — full annotation on UniProt →

Function. Carrier of the growing fatty acid chain in fatty acid biosynthesis. Accessory and non-catalytic subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain. Accessory protein, of the core iron-sulfur cluster (ISC) assembly complex, that regulates, in association with LYRM4, the stability and the cysteine desulfurase activity of NFS1 and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU. The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5.

Subunit / interactions. Mammalian complex I is composed of 45 different subunits. Interacts with ETFRF1. Identified in a complex composed of MALSU1, MIEF1 upstream open reading frame protein and NDUFAB1; within the trimeric complex, MIEF1 upstream open reading frame protein functions as a bridging scaffold that interacts with MALSU1 on one side, and with NDUFAB1 on the other side. The complex interacts with the mitochondrial large ribosomal subunit. Interacts with alpha-1-microglobulin chain; this interaction is required for the maintenance of mitochondrial redox homeostasis. Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is a heterohexamer containing two copies of each monomer. Component of the cyteine desulfurase complex composed of NFS1, LYRM4 and NDUFAB1; this complex contributes to the stability and cysteine desulfurase activity of NFS1.

Subcellular location. Mitochondrion.

Post-translational modifications. Phosphopantetheinylation at Ser-112 is essential for interactions with LYR motif-containing proteins.

Miscellaneous. In contrast to other accessory subunits of complex I, NDUFAB1 is the only subunit that is essential for cell viability in HEK293T cells. Since knockout cells lack assembled complex I and die in galactose media, this suggests that the essential role of NDUFAB1 is independent of complex I.

Similarity. Belongs to the acyl carrier protein (ACP) family.

RefSeq proteins (1): NP_004994* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003231	ACP	Family
IPR006162	Ppantetheine_attach_site	PTM
IPR009081	PP-bd_ACP	Domain
IPR036736	ACP-like_sf	Homologous_superfamily

Pfam: PF00550

UniProt features (15 total): helix 5, turn 2, modified residue 2, strand 2, transit peptide 1, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6ODD	X-RAY DIFFRACTION	2
7OF0	ELECTRON MICROSCOPY	2.2
9N51	X-RAY DIFFRACTION	2.31
8QU5	ELECTRON MICROSCOPY	2.42
7OF7	ELECTRON MICROSCOPY	2.5
9N50	X-RAY DIFFRACTION	2.5
7PO4	ELECTRON MICROSCOPY	2.56
7O9M	ELECTRON MICROSCOPY	2.6
9I4I	ELECTRON MICROSCOPY	2.63
9TI4	ELECTRON MICROSCOPY	2.66
7OF2	ELECTRON MICROSCOPY	2.7
7OF3	ELECTRON MICROSCOPY	2.7
9PRA	ELECTRON MICROSCOPY	2.83
7QH7	ELECTRON MICROSCOPY	2.89
7ODR	ELECTRON MICROSCOPY	2.9
7OF5	ELECTRON MICROSCOPY	2.9
8QSJ	ELECTRON MICROSCOPY	3
5OOM	ELECTRON MICROSCOPY	3.03
8PK0	ELECTRON MICROSCOPY	3.03
5OOL	ELECTRON MICROSCOPY	3.06
7QH6	ELECTRON MICROSCOPY	3.08
7A5J	ELECTRON MICROSCOPY	3.1
7O9K	ELECTRON MICROSCOPY	3.1
7ODS	ELECTRON MICROSCOPY	3.1
7ODT	ELECTRON MICROSCOPY	3.1
7OIC	ELECTRON MICROSCOPY	3.1
7A5H	ELECTRON MICROSCOPY	3.3
7OI9	ELECTRON MICROSCOPY	3.3
5XTB	ELECTRON MICROSCOPY	3.4
7PD3	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14561-F1	78.59	0.52

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 (2): 88, 112

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-6799198	Complex I biogenesis
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-9857492	Protein lipoylation
R-HSA-9937383	Mitochondrial ribosome-associated quality control
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 434 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, MODULE_93, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AAGCAAT_MIR137, chr2p25, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, KAAB_FAILED_HEART_ATRIUM_DN, BASSO_B_LYMPHOCYTE_NETWORK, MODULE_151, MODULE_77, MORF_SNRP70

GO Biological Process (10): mitochondrial electron transport, NADH to ubiquinone (GO:0006120), fatty acid biosynthetic process (GO:0006633), aerobic respiration (GO:0009060), protein lipoylation (GO:0009249), iron-sulfur cluster assembly (GO:0016226), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), [2Fe-2S] cluster assembly (GO:0044571), mitochondrial large ribosomal subunit assembly (GO:1902775), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (7): acyl binding (GO:0000035), acyl carrier activity (GO:0000036), structural molecule activity (GO:0005198), fatty acid binding (GO:0005504), calcium ion binding (GO:0005509), mitochondrial large ribosomal subunit binding (GO:0140978), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), mitochondrial membrane (GO:0031966), respiratory chain complex I (GO:0045271), mitochondrial [2Fe-2S] assembly complex (GO:0099128), iron-sulfur cluster assembly complex (GO:1990229)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Metabolism	2
Aerobic respiration and respiratory electron transport	1
Respiratory electron transport	1
Fatty acid metabolism	1
Post-translational protein modification	1
Mitochondrial translation	1
Metabolism of proteins	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
cytoplasm	2
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
cellular respiration	1
peptidyl-lysine modification	1
protein maturation	1
metallo-sulfur cluster assembly	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	1
iron-sulfur cluster assembly	1
ribosomal large subunit assembly	1
mitochondrial ribosome assembly	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
small molecule binding	1
fatty acid biosynthetic process	1
ACP phosphopantetheine attachment site binding	1
phosphopantetheine-dependent carrier activity	1
molecular_function	1
lipid binding	1
monocarboxylic acid binding	1
metal ion binding	1
ribosomal large subunit binding	1
mitochondrial ribosome binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
mitochondrial envelope	1
organelle membrane	1
NADH dehydrogenase complex	1
respiratory chain complex	1

Protein interactions and networks

STRING

5111 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDUFAB1	OXSM	Q9NWU1	971
NDUFAB1	NDUFA2	O43678	934
NDUFAB1	IL1RL2	Q9HB29	885
NDUFAB1	NDUFB3	O43676	851
NDUFAB1	NDUFA6	P56556	851
NDUFAB1	LYRM4	Q9HD34	844
NDUFAB1	NDUFB9	Q9Y6M9	834
NDUFAB1	NDUFB2	O95178	807
NDUFAB1	NDUFB5	O43674	804
NDUFAB1	NDUFB7	P17568	787
NDUFAB1	NFS1	Q9Y697	773
NDUFAB1	NDUFS1	P28331	765
NDUFAB1	NDUFS6	O75380	757
NDUFAB1	NDUFB8	O95169	737
NDUFAB1	NDUFS8	O00217	737

IntAct

220 interactions, top by confidence:

A	B	Type	Score
NDUFAF5	NDUFAF8	psi-mi:“MI:0914”(association)	0.750
LYRM2	NDUFAB1	psi-mi:“MI:0914”(association)	0.730
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
NDUFAB1	SLIRP	psi-mi:“MI:0915”(physical association)	0.680
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
ETFRF1	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
SDHAF3	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
LYRM4	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
LYRM7	NDUFAB1	psi-mi:“MI:0914”(association)	0.640

BioGRID (202): NDUFAB1 (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS), OXSM (Affinity Capture-MS), LYRM4 (Affinity Capture-MS), GLDC (Affinity Capture-MS), LYRM5 (Affinity Capture-MS), NFS1 (Affinity Capture-MS), LYRM7 (Affinity Capture-MS), LYRM2 (Affinity Capture-MS), ATPAF2 (Affinity Capture-MS), NDUFAB1 (Co-fractionation), NDUFAB1 (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K3CNL6, A0A2Z5WA18, A8J353, A8JGV8, B3MRT7, B3NYF7, B4H303, B4IMF6, B4JWR9, B4M375, B4NE93, B4PZ52, B4R3T1, B5DKJ8, O14561, O49078, O76454, O82499, P02902, P08980, P13272, P26291, P27626, P30361, P36177, P52334, P54150, Q00UI6, Q02585, Q05B87, Q0MQC1, Q0MQC2, Q0MQC3, Q38853, Q41228, Q5CC92, Q5CC93, Q5EU90, Q5NTH3, Q5NTH4

Diamond homologs: A1WMX2, A5EXE0, A6T7F4, A7MFR6, A7ZF37, A7ZKJ7, A7ZZ51, A9III0, A9N5L0, B0K1W0, B0K9X7, B1IUH1, B1LI51, B1XA04, B2U527, B2UTR8, B2V6T8, B3EED1, B3QRN4, B3QS74, B3R210, B4S3N7, B4SBB2, B4T328, B4TFH1, B4TTG0, B5BAH9, B5E8U3, B5F911, B5FKB1, B5QXE0, B5RBA6, B5XXH6, B6I9H1, B6JLE2, B7LG27, B7LX28, B7MJ81, B7MTM4, B7NKI6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NDUFAB1	“form complex”	“NADH-ubiquinone oxidoreductase-Mitochondrial respiratory chain complex I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
Complex I biogenesis	13	34.1×	3e-15
Aerobic respiration and respiratory electron transport	19	26.7×	3e-20
Respiratory electron transport	17	25.7×	6e-18
Mitochondrial ribosome-associated quality control	8	15.6×	2e-06
Mitochondrial translation	6	13.1×	2e-04
Mitochondrial translation initiation	6	12.1×	3e-04
Mitochondrial translation elongation	6	12.1×	3e-04
Mitochondrial translation termination	6	10.5×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial respiratory chain complex I assembly	8	39.6×	2e-09
mitochondrial electron transport, NADH to ubiquinone	9	38.9×	2e-10
proton motive force-driven mitochondrial ATP synthesis	12	38.1×	1e-13
aerobic respiration	11	32.8×	5e-12
mitochondrial translation	6	12.6×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	2
Uncertain significance	54
Likely benign	6
Benign	8

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1330210	GRCh37/hg19 2p25.3(chr2:10501-2386917)x1	Pathogenic
146223	GRCh38/hg38 2p25.3(chr2:30341-3449132)x1	Pathogenic
146260	GRCh38/hg38 2p25.3(chr2:30341-1969402)x1	Pathogenic
147583	GRCh38/hg38 2p25.3(chr2:39193-1542734)x1	Pathogenic
148175	GRCh38/hg38 2p25.3(chr2:30341-2656139)x1	Pathogenic
148269	GRCh38/hg38 2p25.3-23.3(chr2:17019-26318846)x3	Pathogenic
150293	GRCh38/hg38 2p25.3(chr2:24400-817581)x3	Pathogenic
152888	GRCh38/hg38 2p25.3(chr2:17019-2305267)x1	Pathogenic
153475	GRCh38/hg38 2p25.3(chr2:12770-2748672)x1	Pathogenic
154817	GRCh38/hg38 2p25.3(chr2:131730-2713517)x1	Pathogenic
160975	GRCh38/hg38 2p25.3(chr2:30341-507042)x3	Pathogenic
1808728	GRCh37/hg19 2p25.3(chr2:12771-1947832)x1	Pathogenic
2426865	NC_000016.9:g.(?23584033)(23647150_?)del	Pathogenic
2671972	GRCh37/hg19 2p25.3(chr2:12770-2832894)x1	Pathogenic
3242306	GRCh37/hg19 2p25.3(chr2:11314-3033976)x1	Pathogenic
442997	GRCh37/hg19 2p25.3-q37.3(chr2:12771-242783384)x3	Pathogenic
443675	GRCh37/hg19 2p25.3-24.1(chr2:12770-20081474)x3	Pathogenic
4526718	NC_000002.12:g.100000_1793802del	Pathogenic
562667	GRCh37/hg19 2p25.3-25.2(chr2:12770-4823625)x3	Pathogenic
59131	GRCh38/hg38 2p25.3-24.3(chr2:30342-14866951)x3	Pathogenic
59132	GRCh38/hg38 2p25.3-25.1(chr2:50661-9652907)x3	Pathogenic
686001	GRCh37/hg19 2p25.3(chr2:12770-2832894)x1	Pathogenic
686548	GRCh37/hg19 2p25.3-25.1(chr2:12770-7502796)x3	Pathogenic
686549	GRCh37/hg19 2p25.3-25.1(chr2:12770-7502796)x3	Pathogenic
688279	GRCh37/hg19 2p25.3(chr2:12770-2348876)x1	Pathogenic
814206	GRCh37/hg19 2p25.3(chr2:12770-3000954)x1	Pathogenic
148892	GRCh38/hg38 2p25.3(chr2:17019-1645317)x1	Likely pathogenic
152440	GRCh38/hg38 2p25.3-25.2(chr2:17019-4957745)x3	Likely pathogenic

SpliceAI

876 predictions. Top by Δscore:

Variant	Effect	Δscore
16:23581174:C:CA	acceptor_loss	1.0000
16:23581174:C:CC	acceptor_gain	1.0000
16:23582297:T:TA	donor_gain	1.0000
16:23582374:CC:C	acceptor_gain	1.0000
16:23582375:CC:C	acceptor_gain	1.0000
16:23582376:C:CC	acceptor_gain	1.0000
16:23582376:C:T	acceptor_gain	1.0000
16:23585329:GCCTT:G	donor_loss	1.0000
16:23585330:CCTTA:C	donor_loss	1.0000
16:23585332:TTACC:T	donor_loss	1.0000
16:23585333:TA:T	donor_loss	1.0000
16:23585335:C:CG	donor_loss	1.0000
16:23585419:GAAAG:G	acceptor_gain	1.0000
16:23585421:AAG:A	acceptor_gain	1.0000
16:23585422:AG:A	acceptor_gain	1.0000
16:23585423:GC:G	acceptor_loss	1.0000
16:23585424:C:A	acceptor_loss	1.0000
16:23585424:C:CC	acceptor_gain	1.0000
16:23587318:ACCTA:A	acceptor_loss	1.0000
16:23587320:C:CA	acceptor_loss	1.0000
16:23587321:T:G	acceptor_loss	1.0000
16:23581169:AGGGT:A	acceptor_gain	0.9900
16:23581170:GGGT:G	acceptor_gain	0.9900
16:23581171:GGT:G	acceptor_gain	0.9900
16:23581172:GT:G	acceptor_gain	0.9900
16:23581175:T:C	acceptor_loss	0.9900
16:23582271:TTTAC:T	donor_loss	0.9900
16:23582272:TTA:T	donor_loss	0.9900
16:23582273:TA:T	donor_loss	0.9900
16:23582274:ACCT:A	donor_loss	0.9900

AlphaMissense

1015 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:23582366:A:G	I130T	0.998
16:23585337:A:C	F126L	0.998
16:23585337:A:T	F126L	0.998
16:23585339:A:G	F126L	0.998
16:23582342:A:G	L138S	0.997
16:23585346:T:A	E123D	0.997
16:23585346:T:G	E123D	0.997
16:23585377:A:G	L113S	0.997
16:23585379:A:C	S112R	0.997
16:23585379:A:T	S112R	0.997
16:23585381:T:G	S112R	0.997
16:23585386:A:G	L110S	0.997
16:23585354:C:G	A121P	0.996
16:23585365:T:A	E117V	0.996
16:23585404:A:G	F104S	0.996
16:23582310:C:G	A149P	0.995
16:23582366:A:C	I130S	0.995
16:23585347:T:A	E123V	0.995
16:23582312:A:T	I148N	0.994
16:23582352:C:G	A135P	0.994
16:23585338:A:G	F126S	0.994
16:23585382:G:C	D111E	0.994
16:23585382:G:T	D111E	0.994
16:23585383:T:A	D111V	0.994
16:23585374:T:A	D114V	0.993
16:23585366:C:T	E117K	0.992
16:23585375:C:G	D114H	0.992
16:23585383:T:G	D111A	0.992
16:23587240:A:T	V83D	0.992
16:23582351:G:T	A135D	0.991

dbSNP variants (sampled 300 via entrez): RS1000091514 (16:23589439 C>T), RS1000267490 (16:23582130 T>G), RS1000343721 (16:23587873 G>A), RS1000540966 (16:23594132 C>A,G,T), RS1000572591 (16:23593856 ATTT>A), RS1000575578 (16:23581868 C>G), RS1000703463 (16:23587985 C>G), RS1000805063 (16:23581288 G>A), RS1000856038 (16:23581499 T>C), RS1001623983 (16:23581182 G>C), RS1001690202 (16:23593435 TA>T), RS1001807415 (16:23587031 C>T), RS1001963561 (16:23587345 C>G), RS1002047984 (16:23593543 G>T), RS1002390540 (16:23593092 C>T)

Disease associations

OMIM: gene MIM:603836 | disease phenotypes: MIM:616521, MIM:114480

GenCC curated gene-disease

Mondo (2): intellectual disability, autosomal dominant 39 (MONDO:0014678), hereditary breast carcinoma (MONDO:0016419)

Orphanet (1): Hereditary breast cancer (Orphanet:227535)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000044_5	Bipolar disorder	6.000000e-08
GCST003542_30	Night sleep phenotypes	5.000000e-06
GCST005950_2	Body mass index x sex x age interaction (4df test)	5.000000e-75
GCST005951_193	Body mass index	1.000000e-72
GCST005952_2	Body mass index (age>50)	2.000000e-30
GCST005954_1	Body mass index x age interaction	4.000000e-07
GCST006585_478	Blood protein levels	0.000000e+00
GCST007991_3	Large artery stroke	4.000000e-06
GCST010002_382	Refractive error	6.000000e-25
GCST90002400_553	Plateletcrit	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363065 (PROTEIN COMPLEX), CHEMBL6067057 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11553746	ACP1		0.00	0

ChEMBL bioactivities

10 potent at pChembl≥5 of 20 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.06	IC50	870	nM	R-(+)-MARMIN-6’-UNDECANOATE
6.04	IC50	920	nM	R-(+)-MARMIN-6’-LINOLEATE
5.63	IC50	2350	nM	R-(+)-MARMIN-6’-LINOLEATE
5.57	Kd	2722	nM	CHEMBL5653589
5.57	ED50	2722	nM	CHEMBL5653589
5.51	IC50	3080	nM	R-(+)-MARMIN-6’-OCTANOATE
5.43	IC50	3670	nM	R-(+)-MARMIN-6’-UNDECANOATE
5.43	IC50	3710	nM	R-(+)-MARMIN-6’-OCTANOATE
5.31	IC50	4900	nM	(+)-9’-ISOVALEROXYLARICIRESINOL
5.04	IC50	9100	nM	(+)-9’-ISOVALEROXYLARICIRESINOL

PubChem BioAssay actives

9 with measured affinity, of 30 total; 5 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
[(E,3R)-2-hydroxy-2,6-dimethyl-8-(2-oxochromen-7-yl)oxyoct-6-en-3-yl] undecanoate	739270: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	ic50	0.8700	uM
[(E,3R)-2-hydroxy-2,6-dimethyl-8-(2-oxochromen-7-yl)oxyoct-6-en-3-yl] (9Z,12Z)-octadeca-9,12-dienoate	739270: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	ic50	0.9200	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148842: Binding affinity to human NDUFAB1 incubated for 45 mins by Kinobead based pull down assay	kd	2.7218	uM
[(E,3R)-2-hydroxy-2,6-dimethyl-8-(2-oxochromen-7-yl)oxyoct-6-en-3-yl] octanoate	739270: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	ic50	3.0800	uM
[(2S,3R,4R)-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-3-yl]methyl 3-methylbutanoate	739269: Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1,10-phenanthroline-induced HIF1 activation incubated for 30 mins prior to 1,10-phenanthroline-challenge measured after 16 hrs by luciferase reporter assay	ic50	4.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
Arsenic Trioxide	increases expression	2
Arsenic	increases abundance, increases expression, decreases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases expression	2
shuanghuang shengbai	decreases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Doxorubicin	increases expression	1
Fluorouracil	affects expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2353025	Binding	Inhibition of mitochondrial ETC complex 1 in human T47D cells assessed as inhibition of 1% O2-induced HIF1 activation at 30 uM incubated for 30 mins prior to 1% O2-challenge measured after 16 hrs by luciferase reporter assay	Semisynthetic studies identify mitochondria poisons from botanical dietary supplements–geranyloxycoumarins from Aegle marmelos. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00040222	Not specified	COMPLETED	Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer
NCT02557776	Not specified	COMPLETED	Written Genetic Counseling and Mutation Analysis of BRCA1 and BRCA2 to Patients With Breast Cancer
NCT03495544	Not specified	UNKNOWN	Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
NCT03959267	Not specified	COMPLETED	Testing a Culturally Adapted Telephone Genetic Counseling Intervention
NCT04058418	Not specified	COMPLETED	Specialist Recommendation on FBC (Familial Breast Cancer) Chemoprevention Prescribing
NCT04125914	Not specified	ACTIVE_NOT_RECRUITING	Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families
NCT04169542	Not specified	RECRUITING	Impact of COVID-19 Pandemic on Out-of-Pocket Costs, Lost Wages, and Unemployment in Patients With Breast Cancer Undergoing Breast Surgery
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT07292246	Not specified	RECRUITING	A Prospective CohorT Study of HandX - Assisted ENdoscopic MAstectomy: Feasibility and Safety (ATHENA I Study)
NCT07307664	Not specified	RECRUITING	Increasing Germline Genetic Testing for Patients With Cancer