CFAP99

Summary

CFAP99 (cilia and flagella associated protein 99, HGNC:51180) is a protein-coding gene on chromosome 4p16.3, encoding Cilia- and flagella-associated protein 99 (D6REC4).

Predicted to be located in motile cilium.

Source: NCBI Gene 402160 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 165 total
• MANE Select transcript: NM_001193282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:51180
Approved symbol	CFAP99
Name	cilia and flagella associated protein 99
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000206113
Ensembl biotype	protein_coding
Entrez	402160

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000382849, ENST00000511731, ENST00000514556, ENST00000515732, ENST00000635017, ENST00000860043

RefSeq mRNA: 1 — MANE Select: NM_001193282 NM_001193282

Canonical transcript exons

ENST00000635017 — 16 exons

Exon	Start	End
ENSE00001493543	2418955	2419093
ENSE00003738843	2426459	2426586
ENSE00003789015	2462443	2462605
ENSE00003792081	2452142	2452346
ENSE00003792527	2460037	2460242
ENSE00003792697	2458723	2458864
ENSE00003793187	2449934	2450005
ENSE00003793409	2450947	2451018
ENSE00003795990	2459107	2459258
ENSE00003796244	2436874	2437018
ENSE00003796528	2449670	2449750
ENSE00003798378	2438070	2438164
ENSE00003798605	2451264	2451352
ENSE00003799959	2443130	2443242
ENSE00003800347	2445131	2445308
ENSE00004015273	2462810	2463002

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 93.50.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5229 / max 98.7876, expressed in 191 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46610	0.5165	189
46613	0.0063	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.50	gold quality
left testis	UBERON:0004533	88.46	gold quality
right testis	UBERON:0004534	87.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.39	gold quality
testis	UBERON:0000473	84.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.41	gold quality
right adrenal gland	UBERON:0001233	72.28	gold quality
left adrenal gland cortex	UBERON:0035825	72.10	gold quality
left adrenal gland	UBERON:0001234	71.96	gold quality
right adrenal gland cortex	UBERON:0035827	71.60	gold quality
adrenal cortex	UBERON:0001235	69.78	gold quality
adenohypophysis	UBERON:0002196	69.44	gold quality
pituitary gland	UBERON:0000007	69.36	gold quality
adrenal gland	UBERON:0002369	68.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.72	gold quality
right lung	UBERON:0002167	66.45	gold quality
cerebellar hemisphere	UBERON:0002245	66.38	gold quality
cerebellar cortex	UBERON:0002129	66.20	gold quality
left uterine tube	UBERON:0001303	65.67	gold quality
cerebellum	UBERON:0002037	64.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.43	gold quality
caudate nucleus	UBERON:0001873	62.65	gold quality
nasal cavity mucosa	UBERON:0001826	62.51	gold quality
hypothalamus	UBERON:0001898	62.40	gold quality
nucleus accumbens	UBERON:0001882	62.09	gold quality
right frontal lobe	UBERON:0002810	60.91	gold quality
adrenal tissue	UBERON:0018303	60.52	gold quality
fallopian tube	UBERON:0003889	60.28	gold quality
esophagus squamous epithelium	UBERON:0006920	60.28	gold quality
metanephros cortex	UBERON:0010533	60.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.40

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap99	ENSDARG00000097485
mus_musculus	Cfap99	ENSMUSG00000109572
rattus_norvegicus	Cfap99	ENSRNOG00000058434

Protein

Protein identifiers

Cilia- and flagella-associated protein 99 — D6REC4 (reviewed: D6REC4)

All UniProt accessions (1): D6REC4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell projection. Cilium. Flagellum.

Similarity. Belongs to the CFAP99 family.

RefSeq proteins (1): NP_001180211* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039341	CFAP99	Family

UniProt features (6 total): region of interest 2, coiled-coil region 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-D6REC4-F1	77.28	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, chr4p16, GOCC_MOTILE_CILIUM, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CBX7_TARGET_GENES, E2F5_TARGET_GENES, FOXJ2_TARGET_GENES, FOXN3_TARGET_GENES, SNAI1_TARGET_GENES, TAFAZZIN_TARGET_GENES, ZNF175_TARGET_GENES, ZNF197_TARGET_GENES, ZNF589_TARGET_GENES, ZNF592_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): motile cilium (GO:0031514), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cilium	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP99	RSPH10B	P0C881	594
CFAP99	FARP2	O94887	561
CFAP99	SSNA1	O43805	547
CFAP99	PANK4	Q9NVE7	528
CFAP99	ANKRD7	Q92527	527
CFAP99	CFAP47	Q6ZTR5	520
CFAP99	LRGUK	Q96M69	495
CFAP99	FAM227B	Q96M60	480
CFAP99	ABCF3	Q9NUQ8	475
CFAP99	CFAP70	Q5T0N1	460
CFAP99	CCDC180	Q9P1Z9	447
CFAP99	CCDC70	Q6NSX1	445
CFAP99	CFAP65	Q6ZU64	445
CFAP99	SPATA17	Q96L03	435
CFAP99	UBE2G1	P62253	423

IntAct

0 interactions, top by confidence:

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	158
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3389 predictions. Top by Δscore:

Variant	Effect	Δscore
4:2426693:ATG:A	acceptor_gain	1.0000
4:2426693:ATGG:A	acceptor_gain	1.0000
4:2437015:GAGG:G	donor_gain	1.0000
4:2437017:GG:G	donor_gain	1.0000
4:2437018:GG:G	donor_gain	1.0000
4:2437019:G:GG	donor_gain	1.0000
4:2437019:GTA:G	donor_loss	1.0000
4:2437020:T:A	donor_loss	1.0000
4:2438068:A:AG	acceptor_gain	1.0000
4:2438068:AGT:A	acceptor_gain	1.0000
4:2438069:G:GA	acceptor_gain	1.0000
4:2438069:GT:G	acceptor_gain	1.0000
4:2438069:GTG:G	acceptor_gain	1.0000
4:2438161:CAAGG:C	donor_loss	1.0000
4:2438163:AGGTG:A	donor_loss	1.0000
4:2438164:GGTGA:G	donor_loss	1.0000
4:2438165:GTG:G	donor_loss	1.0000
4:2443239:TGAGG:T	donor_loss	1.0000
4:2443243:G:GA	donor_loss	1.0000
4:2443244:T:A	donor_loss	1.0000
4:2449660:A:AG	acceptor_gain	1.0000
4:2449661:C:G	acceptor_gain	1.0000
4:2449747:CGAG:C	donor_loss	1.0000
4:2449749:AGGT:A	donor_loss	1.0000
4:2449751:GTGAG:G	donor_loss	1.0000
4:2449752:T:A	donor_loss	1.0000
4:2451406:A:T	donor_gain	1.0000
4:2452139:CA:C	acceptor_loss	1.0000
4:2452140:A:AG	acceptor_gain	1.0000
4:2452140:AG:A	acceptor_gain	1.0000

AlphaMissense

4594 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011008 (4:2419669 G>A,C), RS1000059398 (4:2462413 T>G), RS1000064899 (4:2442481 G>C), RS1000081716 (4:2429691 A>C,G), RS1000111453 (4:2462198 A>G), RS10001516 (4:2453935 T>C,G), RS1000171834 (4:2422949 G>A), RS1000174293 (4:2426466 C>T), RS1000188101 (4:2460983 C>T), RS1000309431 (4:2423175 T>C), RS1000331113 (4:2431379 A>T), RS1000338792 (4:2432810 G>C,T), RS1000409639 (4:2460810 C>T), RS1000464486 (4:2460879 C>T), RS1000493401 (4:2427956 G>A)

Disease associations

OMIM: gene `` | 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
GCST004077_7	Cognitive function	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
benzo(e)pyrene	decreases methylation	1
licochalcone B	increases expression	1
Methapyrilene	decreases methylation	1
Methotrexate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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