CFAP91

Summary

CFAP91 (cilia and flagella associated protein 91, HGNC:24010) is a protein-coding gene on chromosome 3q13.33, encoding Cilia- and flagella-associated protein 91 (Q7Z4T9). Involved in sperm flagellum axonemal organization and function.

Involved in axonemal central apparatus assembly and spermatogenesis. Predicted to be located in motile cilium and radial spoke stalk. Implicated in spermatogenic failure 51.

Source: NCBI Gene 89876 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 166 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_033364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24010
Approved symbol	CFAP91
Name	cilia and flagella associated protein 91
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	AAT1, AAT1alpha, SPATA26, CaM-IP2, AAT-1
Ensembl gene	ENSG00000183833
Ensembl biotype	protein_coding
OMIM	609910
Entrez	89876

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 5 protein_coding, 5 retained_intron, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000273390, ENST00000461322, ENST00000463700, ENST00000468630, ENST00000469659, ENST00000470948, ENST00000472117, ENST00000475093, ENST00000475543, ENST00000482573, ENST00000482927, ENST00000482995, ENST00000483134, ENST00000488533, ENST00000496010, ENST00000498167, ENST00000861604, ENST00000861605, ENST00000943296

RefSeq mRNA: 4 — MANE Select: NM_033364 NM_001320316, NM_001320317, NM_001320318, NM_033364

CCDS: CCDS2994

Canonical transcript exons

ENST00000273390 — 18 exons

Exon	Start	End
ENSE00001868043	119765052	119767102
ENSE00003458614	119706809	119706885
ENSE00003475279	119715562	119715743
ENSE00003498177	119732294	119732476
ENSE00003501423	119740549	119740695
ENSE00003507505	119737366	119737482
ENSE00003512854	119707404	119707561
ENSE00003529047	119726171	119726348
ENSE00003540535	119747811	119747902
ENSE00003550906	119733364	119733506
ENSE00003582870	119739255	119739326
ENSE00003589529	119708591	119708674
ENSE00003606785	119730220	119730377
ENSE00003607985	119709839	119709895
ENSE00003611408	119743975	119744196
ENSE00003623386	119750937	119751098
ENSE00003670305	119703022	119703222
ENSE00003680791	119747115	119747263

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 97.61.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7278 / max 144.3667, expressed in 546 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38148	2.7150	545
38152	0.0042	1
38149	0.0040	1
38150	0.0030	2
38151	0.0017	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.61	gold quality
bronchial epithelial cell	CL:0002328	97.33	gold quality
bronchus	UBERON:0002185	96.52	gold quality
oviduct epithelium	UBERON:0004804	95.15	gold quality
pituitary gland	UBERON:0000007	93.36	gold quality
left testis	UBERON:0004533	93.12	gold quality
adenohypophysis	UBERON:0002196	92.99	gold quality
right testis	UBERON:0004534	92.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.72	gold quality
sperm	CL:0000019	91.20	gold quality
testis	UBERON:0000473	90.76	gold quality
body of pancreas	UBERON:0001150	90.60	gold quality
fallopian tube	UBERON:0003889	89.33	gold quality
caput epididymis	UBERON:0004358	89.28	gold quality
epithelial cell of pancreas	CL:0000083	89.20	silver quality
tendon of biceps brachii	UBERON:0008188	89.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.82	gold quality
epithelium of nasopharynx	UBERON:0001951	88.67	gold quality
nasopharynx	UBERON:0001728	88.65	gold quality
pancreatic ductal cell	CL:0002079	88.47	silver quality
spleen	UBERON:0002106	87.62	gold quality
sural nerve	UBERON:0015488	86.20	gold quality
left ovary	UBERON:0002119	84.70	gold quality
pancreas	UBERON:0001264	84.58	gold quality
kidney epithelium	UBERON:0004819	84.46	silver quality
nasal cavity epithelium	UBERON:0005384	83.97	gold quality
right ovary	UBERON:0002118	83.63	gold quality
thyroid gland	UBERON:0002046	83.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.12	gold quality
left lobe of thyroid gland	UBERON:0001120	83.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.44
E-MTAB-6678	no	2.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting CFAP91, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-7156-5P	99.64	68.81	1369

Literature-anchored findings (GeneRIF, showing 4)

• identified a novel AMY-1-binding protein, AAT-1, and determined its expression profiles, genes, and cellular localization; results showed that AAT-1 was specifically expressed in the testis throughout spermatogenesis and was also present in mature sperm (PMID:12223483)
• A hydrophobic groove near the exposed residue 213 allows AAT to entrap gemfibrozil (but not fenofibrate), preventing PPARalpha activation. 2 independent studies support a protective role for AAT in established coronary artery atherogenesis progression. (PMID:12692006)
• Allelic variants of the M2 and A332A haplotypes of the human alpha-1-antitrypsin (AAT) gene are associated with human immunodeficiency virus (HIV) infection in 2 African-based populations from HIV-pandemic sub-Saharan Africa. (PMID:14551891)
• Biallelic variants in MAATS1 encoding CFAP91, a calmodulin-associated and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility. (PMID:32161152)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap91	ENSDARG00000006292
mus_musculus	Cfap91	ENSMUSG00000022805
rattus_norvegicus	Cfap91	ENSRNOG00000002976
drosophila_melanogaster	CG15143	FBGN0032647
drosophila_melanogaster	CG15144	FBGN0032648
drosophila_melanogaster	CG15145	FBGN0032649

Protein

Protein identifiers

Cilia- and flagella-associated protein 91 — Q7Z4T9 (reviewed: Q7Z4T9)

Alternative names: AMY-1-associating protein expressed in testis 1, MYCBP/AMY-1-associated testis-expressed protein 1, Protein MAATS1

All UniProt accessions (5): Q7Z4T9, F8WC74, F8WEV1, F8WF10, H7C5C8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in sperm flagellum axonemal organization and function. May regulate cilium motility through its role in the assembly of the axonemal radial spokes.

Subunit / interactions. Interacts with MYCBP and AKAP1. Part of a complex containing MYCBP, AKAP1 and PRKAR2B. Interacts with CFAP61. Interacts with CFAP70. Does not interact with MYCBP.

Subcellular location. Mitochondrion. Cytoplasm. Cytoskeleton. Cilium axoneme Cytoplasm.

Tissue specificity. Strongly expressed in the liver. Widely expressed, but strongly expressed in all spermatogenesis-related tissues, including the testis, the epithelium of cauda and the corpus epididymis, as well as the spermatid and mature sperm. Also expressed in Leydig cells.

Post-translational modifications. Phosphorylated by PKA.

Disease relevance. Spermatogenic failure 51 (SPGF51) [MIM:619177] An autosomal recessive infertility disorder characterized by asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic abnormalities, including absent, short, bent, coiled and irregular-caliber flagella. Abnormalities of the sperm head, base, and acrosome have also been observed. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced by alternative promoter usage.

Similarity. Belongs to the CFAP91 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q7Z4T9-7	7, AAT-1L	yes
Q7Z4T9-1	1, AAT-1M
Q7Z4T9-2	2
Q7Z4T9-3	3
Q7Z4T9-6	6
Q7Z4T9-8	8
Q7Z4T9-5	5, AAT1-beta

RefSeq proteins (4): NP_001307245, NP_001307246, NP_001307247, NP_203528* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026720	CFAP91	Family
IPR032840	CFAP91_dom	Domain

Pfam: PF14738

UniProt features (19 total): sequence conflict 7, splice variant 7, sequence variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4T9-F1	75.20	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): BENPORATH_ES_WITH_H3K27ME3, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, RFX1_02, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_UP, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_CILIUM

GO Biological Process (4): cilium movement (GO:0003341), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), axonemal central apparatus assembly (GO:1904158)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): mitochondrion (GO:0005739), axoneme (GO:0005930), motile cilium (GO:0031514), radial spoke stalk (GO:0001536), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule-based movement	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
cellular component assembly	1
axoneme assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cilium	1
radial spoke	1
protein-containing complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

734 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP91	MYCBP	Q99417	915
CFAP91	CFAP251	Q8TBY9	817
CFAP91	CFAP61	Q8NHU2	769
CFAP91	PRKAR2B	P31323	762
CFAP91	AKAP1	Q92667	757
CFAP91	TTC29	Q8NA56	646
CFAP91	CFAP43	Q8NDM7	615
CFAP91	CFAP69	A5D8W1	602
CFAP91	RSPH3	Q86UC2	601
CFAP91	CFAP70	Q5T0N1	596
CFAP91	FSIP2	Q5CZC0	582
CFAP91	CFAP44	Q96MT7	581
CFAP91	QRICH2	Q9H0J4	579
CFAP91	DNAH1	Q9P2D7	574
CFAP91	ARMC2	Q8NEN0	571

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CFAP91	DPY30	psi-mi:“MI:0915”(physical association)	0.560
MYCBP	CFAP91	psi-mi:“MI:0915”(physical association)	0.370
MYC		psi-mi:“MI:0914”(association)	0.350
CEP97	CFAP91	psi-mi:“MI:0915”(physical association)	0.000
DISC1	CFAP91	psi-mi:“MI:0915”(physical association)	0.000
DPY30	CFAP91	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	CFAP91	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): MAATS1 (Affinity Capture-MS), MAATS1 (Two-hybrid), MAATS1 (Affinity Capture-MS), MAATS1 (Two-hybrid), MAATS1 (Reconstituted Complex), MYCBP (Affinity Capture-Western), AKAP1 (Affinity Capture-Western), MAATS1 (Reconstituted Complex), AKAP1 (Reconstituted Complex), PRKAR2B (Reconstituted Complex), MAATS1 (Positive Genetic), MAATS1 (Two-hybrid), C1orf189 (Cross-Linking-MS (XL-MS)), MAATS1 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A087WRI3, A2BFC9, A2RRW4, A4QMS7, A6NJV1, A6NL82, A6QPC0, A6QQ68, A8E4X8, A8E5W8, A8QW39, A9JS51, D6REC4, F1P3Y5, G3X6E2, P0C875, Q0VB26, Q1MSJ5, Q2IA00, Q2T9Q3, Q2TA11, Q3UY96, Q494V2, Q497Q6, Q4KKZ1, Q4QR77, Q4R5Y0, Q4R8V8, Q5NC57, Q5ZIH9, Q6J272, Q6PII3, Q6ZQR2, Q6ZVS7, Q7Z4T9, Q8CFW7, Q8N1D5, Q8N6G2, Q8WW14, Q95LR0

Diamond homologs: Q7Z4T9, Q8BRC6, Q95LR0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	131
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
812095	NM_033364.4(CFAP91):c.682+1G>A	Pathogenic
2442160	NM_033364.4(CFAP91):c.1633C>T (p.Gln545Ter)	Likely pathogenic
4845746	NM_033364.4(CFAP91):c.359+1G>A	Likely pathogenic
4845825	NM_033364.4(CFAP91):c.852del (p.Ile285fs)	Likely pathogenic

SpliceAI

2630 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119703218:GTACG:G	donor_gain	1.0000
3:119708589:A:AG	acceptor_gain	1.0000
3:119708590:G:GG	acceptor_gain	1.0000
3:119708590:GAACT:G	acceptor_gain	1.0000
3:119708648:A:T	donor_gain	1.0000
3:119709522:GGCT:G	donor_gain	1.0000
3:119715690:T:TA	donor_gain	1.0000
3:119715691:A:AA	donor_gain	1.0000
3:119726349:G:GG	donor_gain	1.0000
3:119730372:TATC:T	donor_gain	1.0000
3:119730373:ATCA:A	donor_gain	1.0000
3:119737481:AT:A	donor_gain	1.0000
3:119737483:G:GG	donor_gain	1.0000
3:119739249:TTTTA:T	acceptor_loss	1.0000
3:119739250:TTTAG:T	acceptor_loss	1.0000
3:119739251:TTA:T	acceptor_loss	1.0000
3:119739252:TA:T	acceptor_loss	1.0000
3:119739254:GGAA:G	acceptor_gain	1.0000
3:119739327:GTGT:G	donor_gain	1.0000
3:119739329:GT:G	donor_gain	1.0000
3:119739331:G:GG	donor_gain	1.0000
3:119740536:T:TA	acceptor_gain	1.0000
3:119740541:T:A	acceptor_gain	1.0000
3:119740547:A:AG	acceptor_gain	1.0000
3:119740547:A:C	acceptor_loss	1.0000
3:119740548:G:A	acceptor_loss	1.0000
3:119740548:G:GG	acceptor_gain	1.0000
3:119740548:GA:G	acceptor_gain	1.0000
3:119740548:GAT:G	acceptor_gain	1.0000
3:119740648:C:T	donor_gain	1.0000

AlphaMissense

5057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119747199:G:C	A663P	0.994
3:119744128:G:C	A612P	0.990
3:119747152:T:C	L647P	0.990
3:119726222:G:C	R245P	0.987
3:119744123:G:C	R610P	0.987
3:119747187:G:C	A659P	0.987
3:119747842:G:C	A695P	0.987
3:119747852:T:A	V698D	0.987
3:119747864:T:C	L702P	0.986
3:119744101:G:C	A603P	0.985
3:119744114:G:C	R607P	0.985
3:119750969:G:C	A726P	0.985
3:119744054:T:C	L587P	0.983
3:119744063:T:C	L590P	0.983
3:119744147:G:C	R618P	0.983
3:119750970:C:A	A726D	0.983
3:119747223:G:C	A671P	0.982
3:119726231:G:C	R248P	0.981
3:119726218:G:C	A244P	0.978
3:119726320:T:A	W278R	0.976
3:119726320:T:C	W278R	0.976
3:119747860:T:C	F701L	0.975
3:119747862:T:A	F701L	0.975
3:119747862:T:G	F701L	0.975
3:119744108:G:C	R605P	0.974
3:119744144:G:C	R617P	0.973
3:119726322:G:C	W278C	0.972
3:119726322:G:T	W278C	0.972
3:119726331:A:C	R281S	0.970
3:119726331:A:T	R281S	0.970

dbSNP variants (sampled 300 via entrez): RS1000029982 (3:119738964 T>C), RS1000047424 (3:119745620 A>G), RS1000052118 (3:119761511 G>A,C), RS1000058370 (3:119736481 T>C), RS1000105916 (3:119719942 A>C), RS1000236278 (3:119764039 A>T), RS1000527898 (3:119741668 A>G), RS1000581641 (3:119741925 A>G), RS1000609993 (3:119762141 C>T), RS1000625970 (3:119711373 C>T), RS1000658829 (3:119711707 G>A), RS1000696633 (3:119764408 A>G), RS1000697560 (3:119755337 A>G), RS1000698501 (3:119709652 A>G), RS1000705131 (3:119709980 C>A,G)

Disease associations

OMIM: gene MIM:609910 | disease phenotypes: MIM:619177

GenCC curated gene-disease

Mondo (2): spermatogenic failure 51 (MONDO:0030926), male infertility with teratozoospermia due to single gene mutation (MONDO:0018394)

Orphanet (1): Male infertility with teratozoospermia due to single gene mutation (Orphanet:399808)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0012207	Reduced sperm motility
HP:0025437	Macrozoospermia
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0032561	Microcephalic sperm head
HP:0033393	Irregularly shaped sperm tail
HP:0033525	Absent sperm axoneme central pair complex

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006993_4	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	7
trichostatin A	affects cotreatment, decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases methylation, increases mutagenesis	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Poly(amidoamine)	decreases expression	1
MT19c compound	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Malathion	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases expression, increases abundance	1

Clinical trials (associated diseases)

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