MFAP1

Summary

MFAP1 (microfibril associated protein 1, HGNC:7032) is a protein-coding gene on chromosome 15q15.3, encoding Microfibrillar-associated protein 1 (P55081). Involved in pre-mRNA splicing as a component of the spliceosome. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in centrosome; microfibril; and nucleoplasm. Part of U2-type precatalytic spliceosome.

Source: NCBI Gene 4236 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_005926

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7032
Approved symbol	MFAP1
Name	microfibril associated protein 1
Location	15q15.3
Locus type	gene with protein product
Status	Approved
Aliases	AMP
Ensembl gene	ENSG00000140259
Ensembl biotype	protein_coding
OMIM	600215
Entrez	4236

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000267812, ENST00000484386, ENST00000940049, ENST00000964887

RefSeq mRNA: 1 — MANE Select: NM_005926 NM_005926

CCDS: CCDS10105

Canonical transcript exons

ENST00000267812 — 9 exons

Exon	Start	End
ENSE00000941987	43817229	43817448
ENSE00000941988	43814945	43815074
ENSE00000941989	43814501	43814688
ENSE00000941990	43813249	43813357
ENSE00000941992	43812987	43813147
ENSE00000941993	43809755	43809914
ENSE00001259201	43804492	43805276
ENSE00001259206	43824491	43824690
ENSE00003675926	43805376	43805465

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 94.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.2345 / max 1176.9964, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149629	44.6176	1815
149628	2.3586	1166
149627	0.2583	111

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.53	gold quality
hair follicle	UBERON:0002073	93.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.97	gold quality
ventricular zone	UBERON:0003053	92.54	gold quality
cartilage tissue	UBERON:0002418	91.88	gold quality
epithelium of nasopharynx	UBERON:0001951	91.73	gold quality
nasopharynx	UBERON:0001728	91.71	gold quality
amniotic fluid	UBERON:0000173	91.53	gold quality
germinal epithelium of ovary	UBERON:0001304	91.41	gold quality
calcaneal tendon	UBERON:0003701	91.21	gold quality
right adrenal gland	UBERON:0001233	91.00	gold quality
tibialis anterior	UBERON:0001385	90.95	gold quality
sural nerve	UBERON:0015488	90.74	gold quality
right adrenal gland cortex	UBERON:0035827	90.70	gold quality
ganglionic eminence	UBERON:0004023	90.60	gold quality
embryo	UBERON:0000922	90.56	gold quality
islet of Langerhans	UBERON:0000006	90.53	gold quality
upper leg skin	UBERON:0004262	90.34	gold quality
left adrenal gland	UBERON:0001234	90.19	gold quality
skin of hip	UBERON:0001554	90.13	gold quality
cortical plate	UBERON:0005343	90.08	gold quality
oocyte	CL:0000023	90.04	gold quality
descending thoracic aorta	UBERON:0002345	89.82	gold quality
left adrenal gland cortex	UBERON:0035825	89.68	gold quality
periodontal ligament	UBERON:0008266	89.67	gold quality
gingival epithelium	UBERON:0001949	89.57	gold quality
esophagus squamous epithelium	UBERON:0006920	89.57	gold quality
adrenal gland	UBERON:0002369	89.47	gold quality
adrenal tissue	UBERON:0018303	89.33	gold quality
epithelium of esophagus	UBERON:0001976	89.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.91
E-MTAB-6142	no	229.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4, MYC

miRNA regulators (miRDB)

49 targeting MFAP1, 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-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-548AI	99.69	69.24	1494

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• Study identified the human B-specific protein MFAP1 as a putative ortholog of the S. cerevisiae tri-snRNP protein Spp381. In vitro binding studies showed that human MFAP1 and yeast Spp381 bind their respective Prp38 proteins via equivalent interfaces and that they cross-interact with the Prp38 proteins of the respective other species. (PMID:28335716)
• Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability. (PMID:31390568)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfap1	ENSDARG00000018241
mus_musculus	Mfap1b	ENSMUSG00000048222
mus_musculus	Mfap1a	ENSMUSG00000068479
rattus_norvegicus	Mfap1al1	ENSRNOG00000004092
rattus_norvegicus	Mfap1a	ENSRNOG00000065756
drosophila_melanogaster	Mfap1	FBGN0035294

Protein

Protein identifiers

Microfibrillar-associated protein 1 — P55081 (reviewed: P55081)

Alternative names: Spliceosome B complex protein MFAP1

All UniProt accessions (1): P55081

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as a component of the spliceosome.

Subunit / interactions. Component of the spliceosome B complex. Interacts with PRPF38A (via N-terminal interaction domain).

Subcellular location. Nucleus.

Similarity. Belongs to the MFAP1 family.

RefSeq proteins (1): NP_005917* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009730	MFAP1_C	Domain
IPR033194	MFAP1	Family

Pfam: PF06991

UniProt features (39 total): modified residue 11, cross-link 7, compositionally biased region 6, sequence conflict 4, strand 3, region of interest 2, helix 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
5F5S	X-RAY DIFFRACTION	2.4
8H6K	ELECTRON MICROSCOPY	2.7
8Q7N	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
9R3D	ELECTRON MICROSCOPY	3.12
6AHD	ELECTRON MICROSCOPY	3.8
7ABF	ELECTRON MICROSCOPY	3.9
8QZS	ELECTRON MICROSCOPY	4.1
7AAV	ELECTRON MICROSCOPY	4.2
5O9Z	ELECTRON MICROSCOPY	4.5
8QO9	ELECTRON MICROSCOPY	5.29
7ABG	ELECTRON MICROSCOPY	7.8
7ABI	ELECTRON MICROSCOPY	8
9R8V	ELECTRON MICROSCOPY	8.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55081-F1	71.84	0.16

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 (18): 2, 52, 53, 94, 116, 118, 132, 133, 267, 361, 432, 67, 249, 357, 371, 381, 415, 418

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 202 (showing top): MORF_ESPL1, MORF_BUB1, MORF_RRM1, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, GENTILE_UV_HIGH_DOSE_DN, REACTOME_MRNA_SPLICING, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GENTILE_UV_RESPONSE_CLUSTER_D6, ACEVEDO_LIVER_CANCER_UP, DANG_BOUND_BY_MYC

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): microfibril (GO:0001527), nucleus (GO:0005634), nucleoplasm (GO:0005654), U2-type spliceosomal complex (GO:0005684), centrosome (GO:0005813), U2-type precatalytic spliceosome (GO:0071005), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
elastic fiber	1
supramolecular fiber	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
spliceosomal complex	1
centriole	1
microtubule organizing center	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

2336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFAP1	MFAP2	P55001	912
MFAP1	ZMAT2	Q96NC0	905
MFAP1	FBN1	P35555	885
MFAP1	PRPF38A	Q8NAV1	870
MFAP1	MFAP3	P55082	870
MFAP1	SMU1	Q2TAY7	834
MFAP1	SART1	O43290	784
MFAP1	ELN	P15502	763
MFAP1	WBP4	O75554	747
MFAP1	FBN2	P35556	686
MFAP1	TSSK2	Q96PF2	668
MFAP1	TSSK1B	Q9BXA7	649
MFAP1	UBL5	Q9BZL1	571
MFAP1	SNW1	Q13573	535
MFAP1	PRPF31	Q8WWY3	535

IntAct

458 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
ZNF398	MFAP1	psi-mi:“MI:0915”(physical association)	0.780
MFAP1	KATNBL1	psi-mi:“MI:0915”(physical association)	0.780
KATNBL1	MFAP1	psi-mi:“MI:0915”(physical association)	0.780
MFAP1	ZNF398	psi-mi:“MI:0915”(physical association)	0.780
CEP55	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
LDOC1	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
FXR2	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
MFAP1	VPS52	psi-mi:“MI:0915”(physical association)	0.720
BEND7	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
CEP70	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
MFAP1	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
MID2	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
MFAP1	MAD1L1	psi-mi:“MI:0915”(physical association)	0.720
MFAP1	FXR2	psi-mi:“MI:0915”(physical association)	0.720
MFAP1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
VPS52	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
MFAP1	CEP70	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (388): MFAP1 (Two-hybrid), MFAP1 (Two-hybrid), MFAP1 (Two-hybrid), MFAP1 (Two-hybrid), VPS52 (Two-hybrid), TADA2A (Two-hybrid), ZBTB14 (Two-hybrid), COIL (Two-hybrid), MAD1L1 (Two-hybrid), STX11 (Two-hybrid), FXR2 (Two-hybrid), NDC80 (Two-hybrid), MID2 (Two-hybrid), MTUS2 (Two-hybrid), LDOC1 (Two-hybrid)

ESM2 similar proteins: A2YQU8, B8BDW1, C0HKD8, C0HKD9, F4HVZ5, O23174, O48713, O80653, O95391, P0CR52, P0CR53, P55080, P55081, Q02775, Q12035, Q16U25, Q21278, Q21827, Q299F9, Q2VPH1, Q3KQD1, Q3ZBE5, Q4KLV7, Q4R4P2, Q4WEH7, Q4WWR2, Q51LA6, Q54TA0, Q568K9, Q5AU50, Q5B3U2, Q5EA98, Q5U3F2, Q5ZIG2, Q69JZ7, Q6C9T0, Q6K8D9, Q6ZK48, Q7KN79, Q7PYQ5

Diamond homologs: C0HKD8, C0HKD9, P55080, P55081, Q54SU3, Q5EA98, Q93712, Q9P7H6, Q9W062

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	8	8.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

756 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43805370:CCATA:C	donor_loss	1.0000
15:43805371:CATAC:C	donor_loss	1.0000
15:43805372:ATAC:A	donor_loss	1.0000
15:43805373:TAC:T	donor_loss	1.0000
15:43805374:A:AG	donor_loss	1.0000
15:43805375:C:T	donor_loss	1.0000
15:43805462:CATC:C	acceptor_gain	1.0000
15:43805464:TCCT:T	acceptor_loss	1.0000
15:43805465:CCTGT:C	acceptor_loss	1.0000
15:43805466:CT:C	acceptor_loss	1.0000
15:43809749:TCTTA:T	donor_loss	1.0000
15:43809750:CTTA:C	donor_loss	1.0000
15:43809751:TTA:T	donor_loss	1.0000
15:43809752:T:TG	donor_loss	1.0000
15:43809753:A:AC	donor_gain	1.0000
15:43809753:A:AG	donor_loss	1.0000
15:43809754:C:CC	donor_gain	1.0000
15:43809784:T:TA	donor_gain	1.0000
15:43809910:CAAGC:C	acceptor_gain	1.0000
15:43809911:AAGC:A	acceptor_gain	1.0000
15:43809912:AGC:A	acceptor_gain	1.0000
15:43809913:GC:G	acceptor_gain	1.0000
15:43809914:CC:C	acceptor_gain	1.0000
15:43809915:C:CA	acceptor_loss	1.0000
15:43809915:C:CC	acceptor_gain	1.0000
15:43809920:C:CT	acceptor_gain	1.0000
15:43809920:C:T	acceptor_gain	1.0000
15:43809921:A:T	acceptor_gain	1.0000
15:43812974:T:C	donor_gain	1.0000
15:43812978:TTTAC:T	donor_loss	1.0000

AlphaMissense

2908 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43805146:C:T	G423E	1.000
15:43805196:C:A	W406C	1.000
15:43805196:C:G	W406C	1.000
15:43805198:A:G	W406R	1.000
15:43805198:A:T	W406R	1.000
15:43805220:A:C	D398E	1.000
15:43805220:A:T	D398E	1.000
15:43805221:T:A	D398V	1.000
15:43805221:T:C	D398G	1.000
15:43805221:T:G	D398A	1.000
15:43805222:C:A	D398Y	1.000
15:43805222:C:G	D398H	1.000
15:43805224:T:G	Q397P	1.000
15:43805233:A:C	L394R	1.000
15:43805233:A:G	L394P	1.000
15:43805233:A:T	L394H	1.000
15:43805234:G:A	L394F	1.000
15:43805235:G:C	H393Q	1.000
15:43805235:G:T	H393Q	1.000
15:43805236:T:C	H393R	1.000
15:43805237:G:C	H393D	1.000
15:43805242:T:C	Y391C	1.000
15:43805243:A:C	Y391D	1.000
15:43805244:T:A	K390N	1.000
15:43805244:T:G	K390N	1.000
15:43805246:T:C	K390E	1.000
15:43805251:C:G	R388P	1.000
15:43805254:C:A	G387V	1.000
15:43805254:C:T	G387D	1.000
15:43805255:C:G	G387R	1.000

dbSNP variants (sampled 300 via entrez): RS1000096443 (15:43818929 T>C), RS1000228290 (15:43807689 C>T), RS1000232454 (15:43816238 C>A,T), RS1000569734 (15:43818060 C>G), RS1000597408 (15:43806815 T>G), RS1000662336 (15:43807843 C>A), RS1000671894 (15:43812966 T>C), RS1000840249 (15:43804790 A>G), RS1000853036 (15:43825893 A>G), RS1000888081 (15:43819773 T>A), RS1000969289 (15:43806649 C>A,T), RS1001176184 (15:43814137 C>A), RS1001208790 (15:43814432 C>G,T), RS1001268666 (15:43809513 A>G), RS1001343873 (15:43816153 A>G)

Disease associations

OMIM: gene MIM:600215 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004963_11	Lipoprotein phospholipase A2 activity in cardiovascular disease	7.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067453 (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
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Citrinin	affects cotreatment, decreases expression	1
Coumestrol	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Mustard Gas	increases phosphorylation	1
Ribonucleotides	affects binding	1
Trichloroethylene	increases phosphorylation	1
Palmitic Acid	increases phosphorylation	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL5652927	Binding	Binding affinity to human MFAP1 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

Clinical trials (associated diseases)

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